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Bile acid CoA ligase deficiency and defective amidation is an anomaly of bile acid synthesis (see this term) characterized by fat malabsorption, neonatal cholestasis and growth failure. ## Epidemiology Prevalence is unknown. Only 8 cases have been reported. ## Clinical description Patients present with a history of neonatal cholestasis, fat and fat-soluble vitamin malabsorption (rickets or bleeding secondary to hypoprothrombinemia) and growth failure. ## Etiology Several mutations in the bile acid-CoA ligase gene have been found in most patients with this defect. ## Genetic counseling The mode of transmission of these mutations is not known. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Bile acid CoA ligase deficiency and defective amidation

c4274079

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=276066

{"icd-10": ["K76.8"]}

A complex, hereditary, spastic paraplegia characterized by delayed motor development, spasticity, and inability to walk, later progressing to quadriplegia, motor aphasia, bowel and bladder dysfunction. Patients also present with vision problems and mild intellectual disability. The disease affects only males. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

X-linked spastic paraplegia type 16

c1846046

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=100997

{"gard": ["9585"], "mesh": ["C536643"], "omim": ["300266"], "umls": ["C1846046"], "icd-10": ["G11.4"], "synonyms": ["SPG16"]}

Occupational cancer is cancer caused by occupational hazards. Several cancers have been directly tied to occupational hazards, including chimney sweeps' carcinoma, mesothelioma, and others. ## Contents * 1 Common occupational hazards implicated in cancer * 2 Occupational cancers * 3 Epidemiology * 4 Prevention * 5 References ## Common occupational hazards implicated in cancer[edit] Occupational exposure to chemicals, dusts, radiation, and certain industrial processes have been tied to occupational cancer. Exposure to cancer-causing chemicals (carcinogens) may cause mutations that allow cells to grow out of control, causing cancer. Carcinogens in the workplace may include chemicals like anilines, chromates, dinitrotoluenes, arsenic and inorganic arsenic compounds, beryllium and beryllium compounds, cadmium compounds, and nickel compounds.[1] Dusts that can cause cancer leather or wood dusts, asbestos,[2] crystalline forms of silica, coal tar pitch volatiles, coke oven emissions, diesel exhaust and environmental tobacco smoke.[1] sunlight; radon gas; and industrial, medical, or other exposure to ionizing radiation can all cause cancer in the workplace. Industrial processes associated with cancer include aluminum production; iron and steel founding; and underground mining with exposure to uranium or radon. Shift work, which can disturb the circadian rhythm, has also been identified as a risk factor for some forms of cancer, in particular for breast cancer. [3][4][5] Other factors that play a role in cancer include:[6] * Personal characteristics such as age, sex, and race * Family history of cancer * Diet and personal habits such as cigarette smoking and alcohol consumption * The presence of certain medical conditions or past medical treatments, including chemotherapy, radiation treatment, or some immune-system suppressing drugs. * Exposure to cancer-causing agents in the environment (for example, sunlight, radon gas, air pollution, and infectious agents) ## Occupational cancers[edit] Common cancers and their exposures and occupations include:[2] Cancer Source Examples of Occupations Bladder Benzidine, beta-naphthylamine, 4-aminobiphenyl, arsenic Rubber, leather, paving, roofing, printing and textile industries; paint/ dyeing products; chimney sweeping; machinists; hairdressers and barbers; truck drivers Kidney Cadmium, trichloroethylene, herbicides, wood dust Painting; metalworking; petroleum, plastics, and textile industries Larynx Asbestos, wood dust, paint fumes Metal working; petroleum, rubber, plastics, and textile industries Leukemia Formaldehyde, benzene, ethylene oxide, pesticides Rubber manufacturing; oil refining; shoemaking, funeral embalming Liver Arsenic, vinyl chloride, aflatoxins Plastic manufacturing Lung Radon, secondhand smoke, asbestos, arsenic, cadmium, chromium compounds, diesel exhaust, sulfur mustard Rubber manufacturing, paving, roofing, painting, chimney sweeping, iron and steel foundry work, welding Lymphoma Benzene, 1, 3-butadiene, ethylene oxide, herbicides, insecticides Rubber manufacturing, painting, hairdresser or barber Mesothelioma Asbestos Mining, railroad, automotive, plumbing, painting and construction industries; factory workers Nasal cavity and sinus Mustard gas, nickel dust, chromium dust, leather dust, wood dust, radium Textile and baking industry, flour milling, nickel refining, furniture and cabinet builders, shoemaking Skin Arsenic, coal tars, paraffin, certain oils, sunlight Chimney sweeping; outside jobs that involve a lot of sun exposure ## Epidemiology[edit] An estimated 48,000 cancers are diagnosed yearly in the US that come from occupational causes; this represents approximately 4-10% of total cancer in the United States.[7] It is estimated that 19% of cancers globally are attributed to environmental exposures (including work-related exposures).[8] ## Prevention[edit] Many occupational cancers are preventable. Personal protective gear, workplace controls, and worker education can prevent exposure to carcinogens in the workplace. Tobacco smoking has also been shown to increase the risk of work-related cancers; decreasing or abstaining from smoking can decrease cancer risk.[2] Agencies like the US Food and Drug Administration, Environmental Protection Agency, the International Agency for Research on Cancer (IARC) and Occupational Safety and Health Administration have developed safety standards and limits for chemical and radiation exposure.[2] ## References[edit] 1. ^ a b "Carcinogen List". National Institute for Occupational Safety and Health. 2 May 2012. Retrieved 5 January 2014. 2. ^ a b c d "Occupation and Cancer" (PDF). American Cancer Society. January 2016. Retrieved 12 February 2016. 3. ^ Fritschi L (July 2009). "Shift work and cancer". BMJ. 339: b2653. doi:10.1136/bmj.b2653. ISSN 0959-8138. PMID 19605423. S2CID 36132408. 4. ^ Stevens RG, Hansen J, Costa G, Haus E, Kauppinen T, Aronson KJ, et al. (February 2011). "Considerations of circadian impact for defining 'shift work' in cancer studies: IARC Working Group Report". Occup Environ Med. 68 (2): 154–62. doi:10.1136/oem.2009.053512. ISSN 1351-0711. PMID 20962033. S2CID 16553063. 5. ^ Megdal SP, Kroenke CH, Laden F, Pukkala E, Schernhammer ES (September 2005). "Night work and breast cancer risk: a systematic review and meta-analysis". Eur. J. Cancer. 41 (13): 2023–32. doi:10.1016/j.ejca.2005.05.010. PMID 16084719. 6. ^ "CDC - Cancer Policy - NIOSH Workplace Safety and Health Topic". www.cdc.gov. Retrieved 2016-02-12. 7. ^ "Occupational Cancer". National Institute for Occupational Safety and Health. 2 May 2012. Retrieved 5 January 2014. 8. ^ "Environmental and occupational cancers". World Health Organization. Retrieved 2016-02-12. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Occupational cancer

c1335101

wikipedia

https://en.wikipedia.org/wiki/Occupational_cancer

{"wikidata": ["Q2936210"]}

Peeling skin syndrome (PSS) refers to a group of conditions that causes skin to peel and tear easily. The main symptom is continual peeling of the skin. The peeling skin is usually painless. Additional symptoms may depend on the form of PSS. Some people with PSS have itching, redness, and scarring. The symptoms of PSS can appear anytime from birth to adulthood, but usually occur by childhood. There are two forms of PSS. In the generalized form, skin peeling involves most of the body. The generalized form has two subtypes, noninflammatory and inflammatory. There is an acral form in which skin peeling is limited to the hands and feet. PSS is caused by genetic variants in several different genes and is inherited in an autosomal recessive pattern of inheritance. PSS is diagnosed based on the symptoms. Other more common conditions may need to be excluded. Treatment is focused on managing the symptoms. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Peeling skin syndrome

c1849193

gard

https://rarediseases.info.nih.gov/diseases/7347/peeling-skin-syndrome

{"mesh": ["C564818"], "omim": ["270300"], "umls": ["C1849193"], "orphanet": ["817"], "synonyms": ["Keratolysis exfoliativa congenita", "Familial continuous skin peeling", "Skin peeling syndrome", "Deciduous skin", "Familial continuous skin peeling syndrome", "Idiopathic deciduous skin", "Keratosis exfoliativa congenita", "Peeling skin disease", "PSS"]}

Nance-Horan syndrome (NHS) is characterized by the association in male patients of congenital cataracts with microcornea, dental anomalies and facial dysmorphism. ## Epidemiology Prevalence is unknown. NHS is a rare but probably underdiagnosed disorder; 36 families have been reported in the literature. ## Clinical description The ocular problem consists of congenital cataract (100% of cases), bilateral, usually severe, dense and most often total, associated with microcornea (96%), or even microphthalmia. In 93% of the cases, it is responsible for severe visual impairment evidenced by nystagmus (93%), sometimes associated with strabismus (43%). Dental abnormalities, although easily overlooked, are nearly constant, involve permanent and deciduous teeth and are of high diagnostic value. The most frequent are diastema, supernumerary incisors or posterior teeth, which are often impacted, and shape abnormalities (the most typical being screwdriver-shaped teeth). Facial dysmorphism is frequent and characterized by a long face, prognathism, a large nose, with a high nasal bridge, and large often protruding ears. Intellectual impairment is observed in about 30% of cases with inter- and intrafamilial variability. It is usually mild or moderate (80%), without motor delay, but in 20% of cases it is severe/profound and associated with autistic features. In heterozygote females, clinical manifestations are identical to those of affected males but they are attenuated and often limited to infraclinical findings. ## Etiology Causative mutations have been identified in the NHS gene (localized to Xp22.2) and typically result in a truncated protein. The differential expression of two NHS isoforms, NHS-A and NHS-1A, and differences in the subcellular localization of these isoforms may partly explain the various clinical manifestations. ## Diagnostic methods Diagnosis is based on clinical findings as there is no biological marker. The recognition of dental abnormalities requires careful physical and radiological dental examination. ## Differential diagnosis Differential diagnosis includes: X-linked microphthalmia, Lenz syndrome, Oculo-facio-cardio-dental (OFCD) syndrome, and Oculo-cerebro-renal (Lowe) syndrome (see these terms). ## Antenatal diagnosis Molecular study may be performed for the purpose of genetic counseling and antenatal diagnosis. ## Genetic counseling NHS is a genetic condition with X-linked semi-dominant transmission and high penetrance in heterozygote females. ## Management and treatment Ocular abnormalities usually require surgery for cataract extraction although the results are poor. Complications (glaucoma, retinal detachment, etc) are treated medically or surgically depending on the type and severity. The ocular problem requires education appropriate for the degree of visual handicap and often necessitates education in a special school for the visually impaired. Dental anomalies may require orthodontic treatment. Intellectual impairment requires special education. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Nance-Horan syndrome

c0796085

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=627

{"gard": ["7161"], "mesh": ["C538336"], "omim": ["302350"], "umls": ["C0796085"], "icd-10": ["Q87.0"]}

Solid pseudopapillary tumour Other namesSolid pseudopapillary neoplasm, solid pseudopapillary tumour/neoplasm of the pancreas, Frantz's tumour Micrograph of a solid pseudopapillary tumour. H&E stain. SpecialtyOncology A solid pseudopapillary tumour is a low-grade malignant neoplasm of the pancreas of papillary architecture that typically afflicts young women.[1] ## Contents * 1 Signs and symptoms * 2 Anatomy * 2.1 Gross morphology * 2.2 Histomorphology * 2.3 Immunohistochemistry * 3 Diagnosis * 4 Management * 5 See also * 6 References ## Signs and symptoms[edit] Solid pseudopapillary tumours are often asymptomatic and are identified incidentally on imaging performed for unrelated reasons. Less often, they may cause abdominal pain. Solid pseudopapillary tumours tend to occur in women, and most often present in the third decade of life.[citation needed] ## Anatomy[edit] ### Gross morphology[edit] Solid pseudopapillary tumours are typically round, well-demarcated, measuring 2–17 cm in diameter (average 8 cm), with solid and cystic areas with hemorrhage on cut sections.[2] ### Histomorphology[edit] Solid pseudopapillary tumours consist of solid sheets of cells that are focally dyscohesive. The cells in the lesion usually have uniform nuclei with occasional nuclear grooves, eosinophilic or clear cytoplasm and PAS positive eosinophilic intracytoplasmic globules.[3] Necrosis is usually present and, as cell death preferentially occurs distant from blood vessels, lead to the formation of pseudopapillae.[citation needed] ### Immunohistochemistry[edit] Solid pseudopapillary tumours show positive nuclear staining for beta catenin, as well as positive immunostaining for CD10, CD56, vimentin, alpha 1-antitrypsin, and neuron specific enolase; they are negative for chromogranin and pancreatic enzymes.[4][5] ## Diagnosis[edit] The diagnosis of solid pseudopapillary tumour of the pancreas is usually confirmed with endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) of the lesion.[citation needed] ## Management[edit] In most cases, solid pseudopapillary tumours should be resected surgically, as there is a risk of malignancy (cancer).[citation needed] ## See also[edit] * Pancreatic cancer * Pancreatic mucinous cystic neoplasm * Serous cystadenoma of the pancreas ## References[edit] 1. ^ Patil TB, Shrikhande SV, Kanhere HA, Saoji RR, Ramadwar MR, Shukla PJ (2006). "Solid pseudopapillary neoplasm of the pancreas: a single institution experience of 14 cases". HPB. 8 (2): 148–50. doi:10.1080/13651820510035721. PMC 2131425. PMID 18333264. 2. ^ Fletcher CDM (2007). Diagnostic Histopathology of Tumors. I (3rd ed.). Elsevier. p. 478. 3. ^ Serra S, Chetty R (November 2008). "Revision 2: an immunohistochemical approach and evaluation of solid pseudopapillary tumour of the pancreas". J. Clin. Pathol. 61 (11): 1153–9. doi:10.1136/jcp.2008.057828. PMID 18708424. 4. ^ Stömmer P, Kraus J, Stolte M, Giedl J (March 1991). "Solid and cystic pancreatic tumors. Clinical, histochemical, and electron microscopic features in ten cases". Cancer. 67 (6): 1635–41. doi:10.1002/1097-0142(19910315)67:6<1635::aid-cncr2820670627>3.0.co;2-m. PMID 1900454. 5. ^ Pettinato G, Manivel JC, Ravetto C, et al. (November 1992). "Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural, and flow cytometric observations, and a review of the literature". Am. J. Clin. Pathol. 98 (5): 478–88. doi:10.1093/ajcp/98.5.478. PMID 1283055. * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Solid pseudopapillary tumour

c1336029

wikipedia

https://en.wikipedia.org/wiki/Solid_pseudopapillary_tumour

{"umls": ["C1336029"], "orphanet": ["424065"], "wikidata": ["Q7557926"]}

Retinoblastoma (RB) is a rare type of eye cancer in the retina that typically develops before the age of 5. It usually affects only one eye, but 1/3 of children with RB develop cancer in both eyes. The first sign is typically a visible whiteness in the pupil called "cat's eye reflex" or leukocoria, which is particularly noticeable in photographs taken with a flash. Other signs and symptoms include strabismus; persistent eye pain, redness or irritation; and blindness or poor vision in the affected eye(s). Retinoblastoma is caused by mutations in the RB1 gene. In about 60% of people with retinoblastoma, mutations are not inherited and occur only in retinal cells. In the other 40% of individuals, mutations are inherited from a parent in an autosomal dominant pattern and can be found in all body cells. Retinoblastoma that is caused by an inherited mutation is called hereditary retinoblastoma. Hereditary retinoblastoma usually occurs at a younger age than retinoblastoma that is not inherited (15 months vs. 24 months). Retinoblastoma that occurs in only one eye is usually not inherited. Retinoblastoma that occurs in both eyes is thought to be inherited. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Retinoblastoma

c0035335

gard

https://rarediseases.info.nih.gov/diseases/7563/retinoblastoma

{"mesh": ["D012175"], "omim": ["180200"], "orphanet": ["790"], "synonyms": ["RB", "Retinal tumor", "Retinal cancer", "Eye cancer, retinoblastoma"]}

This article is about the infection. For the organism, see Fasciola. Not to be confused with Fasciolopsis. A parasitic worm infection Fasciolosis Other namesFascioliasis, fasciolasis, distomatosis, liver rot Fasciola hepatica SpecialtyInfectious disease, hepatology SymptomsAbdominal pain, nausea, yellow skin ComplicationsPancreatitis, anemia[1] CausesFasciola flatworms Risk factorsEating raw watercress Diagnostic methodStool sample[2] PreventionProper food preparation MedicationTriclabendazole[1] Frequency2 millions[1] Fasciolosis is a parasitic worm infection caused by the common liver fluke Fasciola hepatica as well as by Fasciola gigantica. The disease is a plant-borne trematode zoonosis,[3] and is classified as a neglected tropical disease (NTD).[4][5] It affects humans, but its main host is ruminants such as cattle and sheep.[4] The disease progresses through four distinct phases; an initial incubation phase of between a few days up to three months with little or no symptoms; an invasive or acute phase which may manifest with: fever, malaise, abdominal pain, gastrointestinal symptoms, urticaria, anemia, jaundice, and respiratory symptoms.[6] The disease later progresses to a latent phase with less symptoms and ultimately into a chronic or obstructive phase months to years later.[7][8] In the chronic state the disease causes inflammation of the bile ducts, gall bladder and may cause gall stones as well as fibrosis.[4] While chronic inflammation is connected to increased cancer rates, it is unclear whether fasciolosis is associated with increased cancer risk.[9] Up to half of those infected display no symptoms,[4] and diagnosis is difficult because the worm eggs are often missed in fecal examination.[4] The methods of detection are through fecal examination, parasite-specific antibody detection, or radiological diagnosis, as well as laparotomy. In case of a suspected outbreak it may be useful to keep track of dietary history, which is also useful for exclusion of differential diagnoses.[4] Fecal examination is generally not helpful because the worm eggs can seldom be detected in the chronic phase of the infection. Eggs appear in the feces first between 9–11 weeks post-infection. The cause of this is unknown, and it is also difficult to distinguish between the different species of fasciola as well distinguishing them from echinostomes and Fasciolopsis.[4] Most immunodiagnostic tests detect infection with very high sensitivity, and as concentration drops after treatment, it is a very good diagnostic method.[4] Clinically it is not possible to differentiate from other liver and bile diseases. Radiological methods can detect lesions in both acute and chronic infection, while laparotomy will detect lesions and also occasionally eggs and live worms.[4] Because of the size of the parasite, as adult F. hepatica: 20–30 × 13 mm (0.79–1.18 × 0.51 inches) or adult F. gigantica: 25–75 × 12 mm (0.98–2.95 × 0.47 inches), fasciolosis is a big concern.[4] The amount of symptoms depend on how many worms and what stage the infection is in. The death rate is significant in both cattle (67.55%) and goats (24.61%),[10] but generally low among humans.[citation needed] Treatment with triclabendazole has been highly effective against the adult worms as well as various developing stages.[4][6] Praziquantel is not effective, and older drugs such as bithionol are moderately effective but also cause more side effects. Secondary bacterial infection causing cholangitis has also been a concern and can be treated with antibiotics, and toxaemia may be treated with prednisolone.[4] Humans are infected by eating watergrown plants, primarily wild-grown watercress in Europe or morning glory in Asia. Infection may also occur by drinking contaminated water with floating young fasciola or when using utensils washed with contaminated water.[4] Cultivated plants do not spread the disease in the same capacity. Human infection is rare, even if the infection rate is high among animals. Especially high rates of human infection have been found in Bolivia, Peru and Egypt, and this may be due to consumption of certain foods.[4] No vaccine is available to protect people against Fasciola infection.[11] Preventative measures are primarily treating and immunization of the livestock, which are required to host the live cycle of the worms. Veterinary vaccines are in development, and their use is being considered by a number of countries on account of the risk to human health and economic losses resulting from livestock infection.[4] Other methods include using molluscicides to decrease the number of snails that act as vectors, but it is not practical.[4] Educational methods to decrease consumption of wild watercress and other waterplants has been shown to work in areas with a high disease burden.[4] Fascioliasis occurs in Europe, Africa, the Americas as well as Oceania.[4] Recently, worldwide losses in animal productivity due to fasciolosis were conservatively estimated at over US$3.2 billion per annum.[12] Fasciolosis is now recognized as an emerging human disease: the World Health Organization (WHO) has estimated that 2.4 million people are infected with Fasciola, and a further 180 million are at risk of infection.[13] ## Contents * 1 Signs and symptoms * 1.1 Humans * 1.2 Other animals * 2 Cause * 2.1 Transmission * 2.2 Intermediate hosts * 3 Mechanism * 3.1 Resistance to infection * 4 Diagnosis * 5 Prevention * 6 Treatment * 6.1 Humans * 6.2 Domestic animals * 7 Epidemiology * 7.1 Europe * 7.2 Americas * 7.3 Africa * 7.4 Asia * 7.5 Australia and the Oceania * 8 Other animals * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] ### Humans[edit] Hypertrophia of bile ducts in liver caused by F. hepatica (liver section of an infested goat) Adult flukes Fasciola hepatica in bile ducts (liver of goat) The course of fasciolosis in humans has 4 main phases:[7] * Incubation phase: from the ingestion of metacercariae to the appearance of the first symptoms; time period: few days to 3 months; depends on number of ingested metacercariae and immune status of host * Invasive or acute phase: fluke migration up to the bile ducts. This phase is a result of mechanical destruction of the hepatic tissue and the peritoneum by migrating juvenile flukes causing localized and or generalized toxic and allergic reactions.[14] The major symptoms of this phase are: * Fever: usually the first symptom of the disease; 40–42 °C (104–108 °F) * Abdominal pain * Gastrointestinal disturbances: loss of appetite, flatulence, nausea, diarrhea * Urticaria * Respiratory symptoms (very rare): cough, dyspnoea, chest pain, hemoptysis * Hepatomegaly and splenomegaly * Ascites * Anaemia * Jaundice * Latent phase: This phase can last for months or years. The proportion of asymptomatic subjects in this phase is unknown. They are often discovered during family screening after a patient is diagnosed.[7] * Chronic or obstructive phase: This phase may develop months or years after initial infection. Adult flukes in the bile ducts cause inflammation and hyperplasia of the epithelium. The resulting cholangitis and cholecystitis, combined with the large body of the flukes, are sufficient to cause mechanical obstruction of the biliary duct. In this phase, biliary colic, epigastric pain, fatty food intolerance, nausea, jaundice, pruritus, right upper-quadrant abdominal tenderness, etc., are clinical manifestations indistinguishable from cholangitis, cholecystitis and cholelithiasis of other origins. Hepatic enlargement may be associated with an enlarged spleen or ascites. In case of obstruction, the gall bladder is usually enlarged and edematous with thickening of the wall (Ref: Hepatobiliary Fascioliasis: Sonographic and CT Findings in 87 Patients During the InitialPhase and Long-Term Follow-Up. Adnan Kabaalioglu, Kagan Ceken, Emel Alimoglu, Rabin Saba, Metin Cubuk, Gokhan Arslan, Ali Apaydin. AJR 2007; 189:824–828). Fibrous adhesions of the gall bladder to adjacent organs are common. Lithiasis of the bile duct or gall bladder is frequent and the stones are usually small and multiple.[7] ### Other animals[edit] Clinical signs of fasciolosis are always closely associated with infectious dose (amount of ingested metacercariae). In sheep, as the most common definitive host, clinical presentation is divided into 4 types:[15][16] * Acute Type I Fasciolosis: infectious dose is more than 5000 ingested metacercariae. Sheep suddenly die without any previous clinical signs. Ascites, abdominal haemorrhage, icterus, pallor of membranes, weakness may be observed in sheep. * Acute Type II Fasciolosis: infectious dose is 1000-5,000 ingested metacercariae. As above, sheep die but briefly show pallor, loss of condition and ascites. * Subacute Fasciolosis: infectious dose is 800-1000 ingested metacercariae. Sheep are lethargic, anemic and may die. Weight loss is dominant feature. * Chronic Fasciolosis: infectious dose is 200-800 ingested metacercariae. Asymptomatic or gradual development of bottle jaw and ascites (ventral edema), emaciation, weight loss. In blood, anemia, hypoalbuminemia, and eosinophilia may be observed in all types of fasciolosis.[16] Elevation of liver enzyme activities, such a glutamate dehydrogenase (GLDH), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH), is detected in subacute or chronic fasciolosis from 12 to 15 weeks after ingestion of metacercariae.[17][18] Economical effect of fasciolosis in sheep consists in sudden deaths of animals as well as in reduction of weight gain and wool production.[19][20] In goats and cattle, the clinical manifestation is similar to sheep. However, acquired resistance to F. hepatica infection is well known in adult cattle.[21][22] Calves are susceptible to disease but in excess of 1000 metacercariae are usually required to cause clinical fasciolosis. In this case the disease is similar to sheep and is characterized by weight loss, anemia, hypoalbuminemia and (after infection with 10,000 metacercariae) death.[23] Importance of cattle fasciolosis consist in economic losses caused by condemnation of livers at slaughter and production losses especially due to reduced weight gain.[24] In sheep and sometimes cattle, the damaged liver tissue may become infected by the Clostridium bacteria C. novyi type B. The bacteria will release toxins into the bloodstream resulting in what is known as black disease. There is no cure and death follows quickly. As C. novyi is common in the environment, black disease is found wherever populations of liver flukes and sheep overlap.[25] ## Cause[edit] Immature eggs are discharged in the biliary ducts and in the stool 1\. Eggs become embryonated in water 2, eggs release miracidia 3, which invade a suitable snail intermediate host 4, including the genera Galba, Fossaria and Pseudosuccinea. In the snail the parasites undergo several developmental stages (sporocysts The number 4a, rediae The number 4b, and cercariae The number 4c). The cercariae are released from the snail 5 and encyst as metacercariae on aquatic vegetation or other surfaces. Mammals acquire the infection by eating vegetation containing metacercariae. Humans can become infected by ingesting metacercariae-containing freshwater plants, especially watercress 6. After ingestion, the metacercariae excyst in the duodenum 7 and migrate through the intestinal wall, the peritoneal cavity, and the liver parenchyma into the biliary ducts, where they develop into adults 8. In humans, maturation from metacercariae into adult flukes takes approximately 3 to 4 months. The adult flukes (Fasciola hepatica: up to 30 mm by 13 mm; F. gigantica: up to 75 mm) reside in the large biliary ducts of the mammalian host. Fasciola hepatica infect various animal species, mostly herbivores.[26] Fasciolosis is caused by two digenetic trematodes F. hepatica and F. gigantica. Adult flukes of both species are localized in the bile ducts of the liver or gallbladder. F. hepatica measures 2 to 3 cm and has a cosmopolitan distribution. F. gigantica measures 4 to 10 cm in length and the distribution of the species is limited to the tropics and has been recorded in Africa, the Middle East, Eastern Europe and south and eastern Asia.[27] In domestic livestock in Japan, diploid (2n = 20), triploid (3n = 30) and chimeric flukes (2n/3n) have been described, many of which reproduce parthenogenetically. As a result of this unclear classification, flukes in Japan are normally referred to as Fasciola spp.[28] Recent reports based on mitochondrial genes analysis has shown that Japanese Fasciola spp. is more closely related to F. gigantica than to F. hepatica.[29] In India, a species called F. jacksoni was described in elephants.[30] ### Transmission[edit] Human F. hepatica infection is determined by the presence of the intermediate snail hosts, domestic herbivorous animals, climatic conditions and the dietary habits of man.[31] Sheep, goats and cattle are considered the predominant animal reservoirs. While other animals can be infected, they are usually not very important for human disease transmission. On the other hand, some authors have observed that donkeys and pigs contribute to disease transmission in Bolivia.[32] Among wild animals, it has been demonstrated that the peridomestic rat (Rattus rattus) may play an important role in the spread as well as in the transmission of the parasite in Corsica.[33] In France, nutria (Myocastor coypus) was confirmed as a wild reservoir host of F. hepatica.[34] Humans are infected by ingestion of aquatic plants that contain the infectious cercariae.[35] Several species of aquatic vegetables are known as a vehicle of human infection. In Europe, Nasturtium officinale (common watercress), Nasturtium silvestris, Rorippa amphibia (wild watercress), Taraxacum dens leonis (dandelion leaves), Valerianella olitoria (lamb's lettuce), and Mentha viridis (spearmint) were reported as a source of human infections.[7] In the Northern Bolivian Altiplano, some authors suggested that several aquatic plants such as bero-bero (watercress), algas (algae), kjosco and tortora could act as a source of infection for humans.[36] Because F. hepatica cercariae also encyst on water surface, humans can be infected by drinking of fresh untreated water containing cercariae.[31] In addition, an experimental study suggested that humans consuming raw liver dishes from fresh livers infected with juvenile flukes could become infected.[37] ### Intermediate hosts[edit] Galba truncatula \- the most common intermediate host of F. hepatica in Europe and South America Main articles: Fasciola hepatica § Life cycle, and Fasciola gigantica § Intermediate hosts Intermediate hosts of F. hepatica are freshwater snails from family Lymnaeidae.[27][38] Snails from family Planorbidae act as an intermediate host of F. hepatica very occasionally.[3] ## Mechanism[edit] The development of infection in definitive host is divided into two phases: the parenchymal (migratory) phase and the biliary phase.[15] The parenchymal phase begins when excysted juvenile flukes penetrate the intestinal wall. After the penetration of the intestine, flukes migrate within the abdominal cavity and penetrate the liver or other organs. F. hepatica has a strong predilection for the tissues of the liver.[16] Occasionally, ectopic locations of flukes such as the lungs, diaphragm, intestinal wall, kidneys, and subcutaneous tissue can occur.[23][31] During the migration of flukes, tissues are mechanically destroyed and inflammation appears around migratory tracks of flukes. The second phase (the biliary phase) begins when parasites enter the biliary ducts of the liver. In biliary ducts, flukes mature, feed on blood, and produce eggs. Hypertrophy of biliar ducts associated with obstruction of the lumen occurs as a result of tissue damage. ### Resistance to infection[edit] Mechanisms of resistance have been studied by several authors in different animal species. These studies may help to better understand the immune response to F. hepatica in host and are necessary in development of vaccine against the parasite. It has been established that cattle acquire resistance to challenge infection with F. hepatica and F. gigantica when they have been sensitized with primary patent or drug-abbreviated infection.[21] Resistance to fasciolosis was also documented in rats.[39] On the other hand, sheep and goats are not resistant to re-infection with F. hepatica.[40][41] However, there is evidence that two sheep breeds, in particular Indonesian thin tail sheep and Red maasai sheep, are resistant to F. gigantica.[42][43] No reports concerning the resistance in humans are available. ## Diagnosis[edit] Most immunodiagnostic tests will detect infection and have a sensitivity above 90% during all stages of the diseases. In addition antibody concentration quickly drops post treatment and no antibodies are present one year after treatment, which makes it a very good diagnostic method.[4] In humans, diagnosis of fasciolosis is usually achieved parasitologically by findings the fluke eggs in stool, and immunologically by ELISA and Western blot. Coprological examinations of stool alone are generally not adequate because infected humans have important clinical presentations long before eggs are found in the stools. Moreover, in many human infections, the fluke eggs are often not found in the faeces, even after multiple faecal examinations.[31][44] Furthermore, eggs of F. hepatica, F. gigantica and Fasciolopsis buski are morphologically indistinguishable.[44] Therefore, immunonological methods such ELISA and enzyme-linked immunoelectrotransfer blot, also called Western blot, are the most important methods in diagnosis of F. hepatica infection. These immunological tests are based on detection of species-specific antibodies from sera. The antigenic preparations used have been primarily derived from extracts of excretory/secretory products from adult worms, or with partially purified fractions.[45] Recently, purified native and recombinant antigens have been used, e.g. recombinant F. hepatica cathepsin L-like protease.[46] Methods based on antigen detection (circulating in serum or in faeces) are less frequent. In addition, biochemical and haematological examinations of human sera support the exact diagnosis (eosinophilia, elevation of liver enzymes). Ultrasonography and xray of the abdominal cavity, biopsy of liver, and gallbladder punctuate can also be used (ref: US-guided gallbladder aspiration: a new diagnostic method for biliary fascioliasis. A. Kabaalioglu, A. Apaydin, T. Sindel, E. Lüleci. Eur. Radiol. 9, 880±882 (1999) . False fasciolosis (pseudofasciolosis) refers to the presence of eggs in the stool resulting not from an actual infection but from recent ingestion of infected livers containing eggs. This situation (with its potential for misdiagnosis) can be avoided by having the patient follow a liver-free diet several days before a repeat stool examination.[45] In animals, intravital diagnosis is based predominantly on faeces examinations and immunological methods. However, clinical signs, biochemical and haematological profile, season, climate conditions, epidemiology situation, and examinations of snails must be considered.[15][27] Similarly to humans, faeces examinations are not reliable. Moreover, the fluke eggs are detectable in faeces 8–12 weeks post-infection. In spite of that fact, faecal examination is still the only used diagnostic tool in some countries. While coprological diagnosis of fasciolosis is possible from 8- to 12-week post-infection (WPI), F. hepatica specific-antibodies are recognized using ELISA or Western blot after 2-4 week post-infection.[47][48] Therefore, these methods provide early detection of the infection. ## Prevention[edit] In some areas special control programs are in place or have been planned.[11] The types of control measures depend on the setting (such as epidemiologic, ecologic, and cultural factors).[11] Strict control of the growth and sale of watercress and other edible water plants is important. Individual people can protect themselves by not eating raw watercress and other water plants, especially from endemic grazing areas.[11] Travelers to areas with poor sanitation should avoid food and water that might be contaminated (tainted).[11] Vegetables grown in fields, that might have been irrigated with polluted water, should be thoroughly cooked, as should viscera from potentially infected animals.[11] ## Treatment[edit] ### Humans[edit] Several drugs are effective for fascioliasis, both in humans and in domestic animals. The drug of choice in the treatment of fasciolosis is triclabendazole, a member of the benzimidazole family of anthelmintics.[49] The drug works by preventing the polymerization of the molecule tubulin into the cytoskeletal structures, microtubules. Resistance of F. hepatica to triclabendazole has been recorded in Australia in 1995[50] and Ireland in 1998.[51] Praziquantel treatment is ineffective.[52][53] There are case reports of nitazoxanide being successfully used in human fasciolosis treatment in Mexico.[54] There are also reports of bithionol being used successfully.[55] Nitazoxanide has been found effective in trials, but is currently not recommended.[4] ### Domestic animals[edit] Only clorsulon and albendazole are approved for use in the treatment of domestic animals in the United States, but the available flukicides used worldwide also include triclabendazole, netobimin, closantel, rafoxanide, nitroxynil, and oxyclozanide; however, this list of available drugs has some drawbacks.[56] Closantel, nitroxynil, and oxyclozanide are not effective against young liver flukes and should only be used to treat subacute and chronic infections. Triclabendazole is effective at killing flukes of any age, but only those that cause acute infections; flukes that have remained in the body for long periods of time are becoming resistant to this drug.[57] The timing of treatment is critical for success, and is determined by environmental factors and analysis of the expected distribution and prevalence of the disease. For example, in European countries that have large numbers of sheep, computerized systems predict when fascioliasis is most likely to make the biggest impact on sheep populations and how many sheep will most likely be affected. The predictions are dependent on guessing when environmental conditions that are most conducive to parasite multiplication will occur, such as amount of rainfall, evapotranspiration, and the ratio of wet to dry days in a particular month. If heavy infections are expected to occur, treatment for sheep should begin in September/October, then again in January/February, and finally in April/May; the amount of hatching fluke eggs is minimal during these times because they require a warm, wet environment, making treatment more effective.[56] ## Epidemiology[edit] Human and animal fasciolosis occurs worldwide.[27] While animal fasciolosis is distributed in countries with high cattle and sheep production, human fasciolosis occurs, excepting Western Europe, in developing countries. Fasciolosis occurs only in areas where suitable conditions for intermediate hosts exist. Studies carried out in recent years have shown human fasciolosis to be an important public health problem.[31] Human fasciolosis has been reported from countries in Europe, America, Asia, Africa and Oceania. The incidence of human cases has been increasing in 51 countries of the five continents.[7][8] A global analysis shows that the expected correlation between animal and human fasciolosis only appears at a basic level. High prevalences in humans are not necessarily found in areas where fasciolosis is a great veterinary problem. For instance, in South America, hyperendemics and mesoendemics are found in Bolivia and Peru where the veterinary problem is less important, while in countries such as Uruguay, Argentina and Chile, human fasciolosis is only sporadic or hypoendemic.[8] ### Europe[edit] In Europe, human fasciolosis occur mainly in France, Spain, Portugal, and the former USSR.[8] France is considered an important human endemic area. A total of 5863 cases of human fasciolosis were recorded from nine French hospitals from 1970 to 1982.[58] Concerning the former Soviet Union, almost all reported cases were from the Tajik Republic.[8] Several papers referred to human fasciolosis in Turkey.[59] Recently, serological survey of human fasciolosis was performed in some parts of Turkey. The prevalence of the disease was serologically found to be 3.01% in Antalya Province, and between 0.9 and 6.1% in Isparta Province, Mediterranean region of Turkey.[60] In other European countries, fasciolosis is sporadic and the occurrence of the disease is usually combined with travelling to endemic areas. ### Americas[edit] In North America, the disease is very sporadic. In Mexico, 53 cases have been reported. In Central America, fasciolosis is a human health problem in the Caribbean islands, especially in zones of Puerto Rico and Cuba. Pinar del Río Province and Villa Clara Province are Cuban regions where fasciolosis was hyperendemic. In South America, human fasciolosis is a serious problem in Bolivia, Peru, and Ecuador. These Andean countries are considered to be the area with the highest prevalence of human fasciolosis in the world. Well-known human hyperendemic areas are localized predominately in the high plain called altiplano. In the Northern Bolivian Altiplano, prevalences detected in some communities were up to 72% and 100% in coprological and serological surveys, respectively.[7] In Peru, F. hepatica in humans occurs throughout the country. The highest prevalences were reported in Arequipa, Mantaro Valley, Cajamarca Valley, and Puno Region.[3] In other South American countries like Argentina, Uruguay, Brazil, Venezuela and Colombia, human fasciolosis appear to be sporadic, despite the high prevalences of fasciolosis in cattle. ### Africa[edit] In Africa, human cases of fasciolosis, except in northern parts, have not been frequently reported. The highest prevalence was recorded in Egypt where the disease is distributed in communities living in the Nile Delta.[3] ### Asia[edit] In Asia, the most human cases were reported in Iran, especially in Gīlān Province, on the Caspian Sea. It was mentioned that more than 10,000 human cases were detected in Iran. In eastern Asia, human fasciolosis appears to be sporadic. Few cases were documented in Japan, Koreas, Vietnam, and Thailand.[7] ### Australia and the Oceania[edit] In Australia, human fasciolosis is very rare (only 12 cases documented). In New Zealand, F. hepatica has never been detected in humans.[7] ## Other animals[edit] Formula of triclabendazole A number of drugs have been used in control fasciolosis in animals. Drugs differ in their efficacy, mode of action, price, and viability. Fasciolicides (drugs against Fasciola spp.) fall into five main chemical groups:[61] * Halogenated phenols: bithionol (Bitin), hexachlorophene (Bilevon), nitroxynil (Trodax) * Salicylanilides: closantel (Flukiver, Supaverm), rafoxanide (Flukanide, Ranizole) * Benzimidazoles: triclabendazole (Fasinex), albendazole (Vermitan, Valbazen), mebendazol (Telmin), luxabendazole (Fluxacur) * Sulphonamides: clorsulon (Ivomec Plus) * Phenoxyalkanes: diamphenetide (Coriban) Triclabendazole (Fasinex) is considered as the most common drug due to its high efficacy against adult as well as juvenile flukes. Triclabendazole is used in control of fasciolosis of livestock in many countries. Nevertheless, long-term veterinary use of triclabendazole has caused appearance of resistance in F. hepatica. In animals, triclabendazole resistance was first described in Australia,[62] later in Ireland[63] and Scotland[64] and more recently in the Netherlands.[65] Considering this fact, scientists have started to work on the development of new drug. Recently, a new fasciolicide was successfully tested in naturally and experimentally infected cattle in Mexico. This new drug is called 'Compound Alpha' and is chemically very similar to triclabendazole.[66] Countries where fasciolosis in livestock was repeatedly reported: * Europe: UK, Ireland, France, Portugal, Spain, Switzerland, Italy, Netherlands, Germany, Poland * Asia: Turkey, Russia, Thailand, Iraq, Iran, China, Vietnam, India, Nepal, Japan, Korea, Philippines * Africa: Kenya, Zimbabwe, Nigeria, Egypt, Gambia, Morocco * Australia and the Oceania: Australia, New Zealand * Americas:United States, Mexico, Cuba, Peru, Chile, Uruguay, Argentina, Jamaica, Brazil On September 8, 2007, Veterinary officials in South Cotabato, Philippines said that laboratory tests on samples from cows, carabaos, and horses in the province's 10 towns and lone city showed the level of infection at 89.5%, a sudden increase of positive cases among large livestock due to the erratic weather condition in the area. They must be treated forthwith to prevent complications with surra and hemorrhagic septicemia diseases. 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PMID 7165155. 48. ^ Duménigo BE, Espino AM, Finlay CM, Mezo M (March 2000). "Kinetics of antibody-based antigen detection in serum and faeces of sheep experimentally infected with Fasciola hepatica". Vet. Parasitol. 89 (1–2): 153–61. doi:10.1016/S0304-4017(00)00206-5. PMID 10729655. 49. ^ Savioli L, Chitsulo L, Montresor A (1999). "New opportunities for the control of fascioliasis". Bull. World Health Organ. 77 (4): 300. PMC 2557651. PMID 10327707. 50. ^ Overend DJ & Bowen FL (1995). "Resistance of Fasciola hepatica to triclabendazole". Austral Vet J. 72 (7): 275–276. doi:10.1111/j.1751-0813.1995.tb03546.x. PMID 8534235. 51. ^ Mulcahy G, Dalton JP (1998). "Vaccines in control of liver fluke infections in ruminants: current status and prospects". Irish Vet J. 51: 520–525. 52. ^ Schubert S, Phetsouvanh R (1990). "Praziquantel weitgehend unwirksam: Behandlung des Fasciola-hepatica-Befalles (grosser Leberegel)". Z Arztl Fortbild (Jena). 84 (14): 705–7. PMID 2264356. 53. ^ Price TA, Tuazon CU, Simon GL (1993). "Fascioliasis: case reports and review". Clin Infect Dis. 17 (3): 426–30. doi:10.1093/clinids/17.3.426. PMID 8218685. 54. ^ Rossignol JF, Abaza H, Friedman H (1998). "Successful treatment of human fascioliasis with nitazoxanide". Trans. R. Soc. Trop. Med. Hyg. 92 (1): 103–4. doi:10.1016/S0035-9203(98)90974-9. PMID 9692168. 55. ^ Ramachandran, A. (2000). Pharmacology Recall. 56. ^ a b Ballweber, L. (2018). Fasciola hepatica in ruminants. Merck vet manual (1.2) 57. ^ "NADIS Animal Health Skills - Liver Fluke Control in Sheep". www.nadis.org.uk. Retrieved 2019-09-07. 58. ^ Danis, M., Nozais, J.P., Chandenier, J., 1985. "La distomatose à Fasciola hepatica, II: La fasciolose humaine en France". Action Vet. 907. 59. ^ Yilmaz H, Gödekmerdan A (October 2004). "Human fasciolosis in Van Province, Turkey". Acta Trop. 92 (2): 161–2. doi:10.1016/j.actatropica.2004.04.009. PMID 15350869. 60. ^ Demirci, M., 2003. Insanlarda epidemiyoloji. In: Tinar, R., Korkmaz, M. (Eds.), Fasciolosis. Türkiye Parazitoloji Derněgi, META Basim, İzmir, pp. 343–358 (in Turkish). 61. ^ Fairweather I, Boray JC (September 1999). "Fasciolicides: efficacy, actions, resistance and its management". Vet. J. 158 (2): 81–112. doi:10.1053/tvjl.1999.0377. PMID 10489266. 62. ^ Overend DJ, Bowen FL (July 1995). "Resistance of Fasciola hepatica to triclabendazole". Aust. Vet. J. 72 (7): 275–6. doi:10.1111/j.1751-0813.1995.tb03546.x. PMID 8534235. 63. ^ O’Brien, D.J., 1998. Fasciolosis: a threat to livestock. Irish Vet. J. 51, 539–541. 64. ^ Mitchell GB, Maris L, Bonniwell MA (October 1998). "Triclabendazole-resistant liver fluke in Scottish sheep". Vet. Rec. 143 (14): 399. PMID 9802201. 65. ^ Moll L, Gaasenbeek CP, Vellema P, Borgsteede FH (July 2000). "Resistance of Fasciola hepatica against triclabendazole in cattle and sheep in The netherlands". Vet. Parasitol. 91 (1–2): 153–8. doi:10.1016/S0304-4017(00)00267-3. PMID 10889368. 66. ^ Ibarra F, Vera Y, Quiroz H, et al. (February 2004). "Determination of the effective dose of an experimental fasciolicide in naturally and experimentally infected cattle". Vet. Parasitol. 120 (1–2): 65–74. doi:10.1016/j.vetpar.2003.12.005. PMID 15019144. 67. ^ GMA NEWS.TV, Rise in animal liver fluke cases alarms South Cotabato ## External links[edit] Classification D * ICD-10: B66.3 * ICD-9-CM: 121.3 * MeSH: D005211 * DiseasesDB: 4757 External resources * eMedicine: ped/760 * Fasciolosis Overview at CDC * Immunodiagnosis of fasciolosis in Bolivian Altiplano * Fasciolosis * Pictures of adult flukes * Pictures of F. hepatica eggs * v * t * e Parasitic disease caused by helminthiases Flatworm/ platyhelminth infection Fluke/trematode (Trematode infection) Blood fluke * Schistosoma mansoni / S. japonicum / S. mekongi / S. haematobium / S. intercalatum * Schistosomiasis * Trichobilharzia regenti * Swimmer's itch Liver fluke * Clonorchis sinensis * Clonorchiasis * Dicrocoelium dendriticum / D. hospes * Dicrocoeliasis * Fasciola hepatica / F. gigantica * Fasciolosis * Opisthorchis viverrini / O. felineus * Opisthorchiasis Lung fluke * Paragonimus westermani / P. kellicotti * Paragonimiasis Intestinal fluke * Fasciolopsis buski * Fasciolopsiasis * Metagonimus yokogawai * Metagonimiasis * Heterophyes heterophyes * Heterophyiasis Cestoda (Tapeworm infection) Cyclophyllidea * Echinococcus granulosus / E. multilocularis * Echinococcosis * Taenia saginata / T. asiatica / T. solium (pork) * Taeniasis / Cysticercosis * Hymenolepis nana / H. diminuta * Hymenolepiasis Pseudophyllidea * Diphyllobothrium latum * Diphyllobothriasis * Spirometra erinaceieuropaei * Sparganosis * Diphyllobothrium mansonoides * Sparganosis Roundworm/ Nematode infection Secernentea Spiruria Camallanida * Dracunculus medinensis * Dracunculiasis Spirurida Filarioidea (Filariasis) * Onchocerca volvulus * Onchocerciasis * Loa loa * Loa loa filariasis * Mansonella * Mansonelliasis * Dirofilaria repens * D. immitis * Dirofilariasis * Wuchereria bancrofti / Brugia malayi / |B. timori * Lymphatic filariasis Thelazioidea * Gnathostoma spinigerum / G. hispidum * Gnathostomiasis * Thelazia * Thelaziasis Spiruroidea * Gongylonema Strongylida (hookworm) * Hookworm infection * Ancylostoma duodenale / A. braziliense * Ancylostomiasis / Cutaneous larva migrans * Necator americanus * Necatoriasis * Angiostrongylus cantonensis * Angiostrongyliasis * Metastrongylus * Metastrongylosis Ascaridida * Ascaris lumbricoides * Ascariasis * Anisakis * Anisakiasis * Toxocara canis / T. cati * Visceral larva migrans / Toxocariasis * Baylisascaris * Dioctophyme renale * Dioctophymosis * Parascaris equorum Rhabditida * Strongyloides stercoralis * Strongyloidiasis * Trichostrongylus spp. * Trichostrongyliasis * Halicephalobus gingivalis Oxyurida * Enterobius vermicularis * Enterobiasis Adenophorea * Trichinella spiralis * Trichinosis * Trichuris trichiura (Trichuriasis / Whipworm) * Capillaria philippinensis * Intestinal capillariasis * C. hepatica *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Fasciolosis

c0015652

wikipedia

https://en.wikipedia.org/wiki/Fasciolosis

{"gard": ["6428"], "mesh": ["D005211"], "umls": ["C0015652"], "wikidata": ["Q6972442"]}

Donnai Barrow syndrome is an inherited disorder that affects many parts of the body. People with this condition generally have characteristic facial features, severe sensorineural hearing loss, vision problems and an absent or underdeveloped corpus callosum (the tissue connecting the left and right halves of the brain). Other features may include diaphragmatic hernia, omphalocele, and/or other abnormalities of the intestine or heart. Affected people often have mild to moderate intellectual disability and developmental delay. Donnai Barrow syndrome is caused by changes (mutations) in the LRP2 gene and is inherited in an autosomal recessive manner. Treatment of this condition is based on the signs and symptoms present in each person but may include hearing aids and/or cochlear implants for hearing loss, corrective lenses for vision problems and surgery for certain physical abnormalities. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Donnai-Barrow syndrome

c1857277

gard

https://rarediseases.info.nih.gov/diseases/1899/donnai-barrow-syndrome

{"mesh": ["C536390"], "omim": ["222448"], "umls": ["C1857277"], "orphanet": ["2143"], "synonyms": ["Faciooculoacousticorenal syndrome", "DBS/FOAR syndrome", "Diaphragmatic hernia exomphalos absent corpus callosum hypertelorism myopia sensorineural deafness and proteinuria"]}

Third-degree atrioventricular block Other namesComplete heart block 12-lead ECG showing complete heart block SpecialtyCardiology SymptomsDizziness, Fainting, Shortness of breath CausesFibrosis in cardiac conduction system, myocardial infarction, post-cardiac surgery, medication, vagal tone, electrolyte disturbances Diagnostic methodElectrocardiogram TreatmentPacemaker Third-degree atrioventricular block (AV block) is a medical condition in which the nerve impulse generated in the sinoatrial node (SA node) in the atrium of the heart can not propagate to the ventricles.[1] Because the impulse is blocked, an accessory pacemaker in the lower chambers will typically activate the ventricles. This is known as an escape rhythm. Since this accessory pacemaker also activates independently of the impulse generated at the SA node, two independent rhythms can be noted on the electrocardiogram (ECG). * The P waves with a regular P-to-P interval (in other words, a sinus rhythm) represent the first rhythm. * The QRS complexes with a regular R-to-R interval represent the second rhythm. The PR interval will be variable, as the hallmark of complete heart block is lack of any apparent relationship between P waves and QRS complexes. ## Contents * 1 Presentation * 2 Cause * 3 Treatment * 4 Intervention * 5 Prognosis * 6 See also * 7 References * 8 External links ## Presentation[edit] People with third-degree AV block typically experience severe bradycardia (an abnormally low measured heart rate), hypotension, and at times, hemodynamic instability.[2] ## Cause[edit] Leads I and II demonstrating complete AV block. Note that the P waves are not related to the QRS complexes (PP interval and QRS interval both constant), demonstrating that the atria are electrically disconnected from the ventricles. The QRS complexes represent an escape rhythm arising from the ventricle. Atrial tachycardia with complete A-V block and resulting junctional escape Many conditions can cause third-degree heart block, but the most common cause is coronary ischemia. Progressive degeneration of the electrical conduction system of the heart can lead to third-degree heart block. This may be preceded by first-degree AV block, second-degree AV block, bundle branch block, or bifascicular block. In addition, acute myocardial infarction may present with third-degree AV block. An inferior wall myocardial infarction may cause damage to the AV node, causing third-degree heart block. In this case, the damage is usually transitory. Studies have shown that third-degree heart block in the setting of an inferior wall myocardial infarction typically resolves within 2 weeks.[3] The escape rhythm typically originates in the AV junction, producing a narrow complex escape rhythm. An anterior wall myocardial infarction may damage the distal conduction system of the heart, causing third-degree heart block. This is typically extensive, permanent damage to the conduction system, necessitating a permanent pacemaker to be placed.[4] The escape rhythm typically originates in the ventricles, producing a wide complex escape rhythm. Third-degree heart block may also be congenital and has been linked to the presence of lupus in the mother.[5] It is thought that maternal antibodies may cross the placenta and attack the heart tissue during gestation. The cause of congenital third-degree heart block in many patients is unknown. Studies suggest that the prevalence of congenital third-degree heart block is between 1 in 15,000 and 1 in 22,000 live births. Hyperkalemia in those with previous cardiac disease[6] and Lyme disease can also result in third-degree heart block.[7] ## Treatment[edit] Atropine is often used as a first line treatment of a third-degree heart block in the presence of a narrow QRS which indicates a nodal block, but, may have little to no effect in an infra-nodal block.[8] Atropine works by reducing vagal stimulation through the AV node but will not be effective in those who have had a previous heart transplant.[9] Other drugs may be utilized such as epinephrine or dopamine which have positive chronotropic effects and may increase the heart rate.[10] Treatment in emergency situations can involve electrical transcutaneous pacing in those who are acutely hemodynamically unstable and can be used regardless of the persons level of consciousness.[11] Sedative agents such as a benzodiazapine or opiate may be used in conjunction with transcutaneous pacing to reduce the pain caused by the intervention.[10][11] In cases of suspected beta-blocker overdose, the heart-block may be treated with pharmacological agents to reverse the underlying cause with the use of glucagon. In the case of a calcium channel blocker overdose treated with calcium chloride and digitalis toxicity may be treated with the digoxin immune Fab.[12] Third-degree AV block can be treated more permanently with the use of a dual-chamber artificial pacemaker.[13] This type of device typically listens for a pulse from the SA node via lead in the right atrium and sends a pulse via a lead to the right ventricle at an appropriate delay, driving both the right and left ventricles. Pacemakers in this role are usually programmed to enforce a minimum heart rate and to record instances of atrial flutter and atrial fibrillation, two common secondary conditions that can accompany third-degree AV block. Since pacemaker correction of third-degree block requires full-time pacing of the ventricles, a potential side effect is pacemaker syndrome, and may necessitate use of a biventricular pacemaker, which has an additional 3rd lead placed in a vein in the left ventricle, providing a more coordinated pacing of both ventricles. The 2005 Joint European Resuscitation and Resuscitation Council (UK) guidelines[14] state that atropine is the first line treatment especially if there were any adverse signs, namely: 1) heart rate < 40 bpm, 2) systolic blood pressure < 100 mm Hg, 3) signs of heart failure, and 4) ventricular arrhythmias requiring suppression. If these fail to respond to atropine or there is a potential risk of asystole, transvenous pacing is indicated. The risk factors for asystole include 1) previous asystole, 2) complete heart block with wide complexes, and 3) ventricular pause for > 3 seconds. Mobitz Type 2 AV block is another indication for pacing. As with other forms of heart block, secondary prevention may also include medicines to control blood pressure and atrial fibrillation, as well as lifestyle and dietary changes to reduce risk factors associated with heart attack and stroke. ## Intervention[edit] Early treatment of atrioventricular blockade is based on the presence and severity of symptoms and signs associated with ventricular escape rhythm. Hemodynamically unstable patients require immediate medication and in most cases temporary pacing to increase heart rate and cardiac output. Once the patient is hemodynamically stable, a potentially reversible cause should be evaluated and treated. If no reversible cause is identified, a permanent pacemaker is inserted.[citation needed] Most stable patients have persistent bradycardia-related symptoms and require identification and treatment of any reversible cause or permanent implantable pacemaker. Reversible causes of complete AV block should be ruled out before the insertion of a permanent pacemaker, such as drugs that slows heart rate and which induce hyperkalemia. Complete atrioventricular block in acute myocardial infarction should be treated with temporary pacing and revascularization.[citation needed] Complete atrioventricular block caused by hyperkalemia should be treated to lower serum potassium levels and patients with hypothyroidism should also receive thyroid hormone.[citation needed] If there is no reversible cause, the clear treatment of complete atrioventricular block is mostly permanent pacemaker placement.[citation needed] ## Prognosis[edit] The prognosis of patients with complete heart block is generally poor without therapy. Patients with 1st and 2nd degree heart block are usually asymptomatic.[15] ## See also[edit] * Cardiac pacemaker * Electrical conduction system of the heart * Electrocardiogram (ECG) * Atrioventricular block * First-degree AV block * Second-degree AV block ## References[edit] 1. ^ "ECG Conduction Abnormalities". Retrieved 2009-01-07. 2. ^ "Heart Block". NHS Choices. National Health Service (UK). Retrieved 25 August 2015. 3. ^ Sclarovsky, S; Strasberg, B; Hirshberg, A; Arditi, A; Lewin, RF; Agmon, J (July 1984). "Advanced early and late atrioventricular block in acute inferior wall myocardial infarction". American Heart Journal. 108 (1): 19–24. doi:10.1016/0002-8703(84)90539-8. PMID 6731277. 4. ^ Dorney, E (September 1981). "The role of pacemaker therapy in acute myocardial infarction". Primary Care. 8 (3): 509–17. PMID 7031733. 5. ^ Brucato, A; Previtali, E; Ramoni, V; Ghidoni, S (September 2010). "Arrhythmias presenting in neonatal lupus" (PDF). Scandinavian Journal of Immunology. 72 (3): 198–204. doi:10.1111/j.1365-3083.2010.02441.x. hdl:2434/635678. PMID 20696016. 6. ^ Sohoni A, Perez B, Singh A (2010). "Wenckebach Block due to Hyperkalemia: A Case Report". Emerg Med Int. 2010: 879751. doi:10.1155/2010/879751. PMC 3200192. PMID 22046534. 7. ^ Forrester, JD; Mead, P (October 2014). "Third-degree heart block associated with lyme carditis: review of published cases". Clinical Infectious Diseases. 59 (7): 996–1000. doi:10.1093/cid/ciu411. PMID 24879781. 8. ^ Tintinalli's emergency medicine : a comprehensive study guide. Tintinalli, Judith E.,, Stapczynski, J. Stephan,, Ma, O. John,, Yealy, Donald M.,, Meckler, Garth D.,, Cline, David, 1956- (Eighth ed.). New York. 2015-11-10. p. 123. ISBN 9780071794763. OCLC 915775025.CS1 maint: others (link) 9. ^ "Third-Degree Atrioventricular Block (Complete Heart Block) Treatment & Management: Approach Considerations, Initial Management Considerations, Atropine and Transcutaneous/Transvenous Pacing". 2018-07-05. Cite journal requires `|journal=` (help) 10. ^ a b Oxford textbook of critical care. Webb, Andrew R. (Andrew Roy),, Angus, D. C. (Derek C.), 1962-, Finfer, Simon,, Gattinoni, Luciano,, Singer, Mervyn (Second ed.). Oxford. 2016-05-26. pp. 730–735. ISBN 9780199600830. OCLC 954059445.CS1 maint: others (link) 11. ^ a b Rosen's emergency medicine : concepts and clinical practice. Walls, Ron M.,, Hockberger, Robert S.,, Gausche-Hill, Marianne (Ninth ed.). Philadelphia, PA. 2017-03-09. p. 959. ISBN 9780323390163. OCLC 989157341.CS1 maint: others (link) 12. ^ "Atrioventricular block, Treatment Options". BMJ Best Practice. BMJ (British Medical Journal). Retrieved 25 August 2015. 13. ^ Dretzke, J.; et al. "Compared to single chamber ventricular pacemakers, dual chamber pacemakers may reduce the incidence of complications in people with sick sinus syndrome and atrioventricular block". Cochrane reviews. Retrieved 25 August 2015. 14. ^ "Peri-arrest arrhythmias". Resuscitation guidelines. Resuscitation Council UK. Retrieved 25 August 2015. 15. ^ Edhag O, Swahn A (1976). "Prognosis of patients with complete heart block or arrhythmic syncope who were not treated with artificial pacemakers. A long-term follow-up study of 101 patients". Acta Med Scand. 200 (6): 457–63. doi:10.1111/j.0954-6820.1976.tb08264.x. PMID 1015354. ## External links[edit] Classification D * ICD-10: I44.2 * ICD-9-CM: 426.0 * DiseasesDB: 10477 External resources * eMedicine: emerg/235 * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Third-degree atrioventricular block

c0151517

wikipedia

https://en.wikipedia.org/wiki/Third-degree_atrioventricular_block

{"umls": ["C0151517"], "icd-9": ["426.0"], "icd-10": ["I44.2"], "wikidata": ["Q3640984"]}

MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is an inherited disorder that can cause liver disease and neurological problems. The signs and symptoms of this condition begin in infancy and typically include vomiting, diarrhea, and an inability to grow or gain weight at the expected rate (failure to thrive). Many affected infants have a buildup of a chemical called lactic acid in the body (lactic acidosis) and low blood sugar (hypoglycemia). Within the first weeks of life, infants develop liver disease that quickly progresses to liver failure. The liver is frequently enlarged (hepatomegaly) and liver cells often have a reduced ability to release a digestive fluid called bile (cholestasis). Rarely, affected children develop liver cancer. After the onset of liver disease, many affected infants develop neurological problems, which can include developmental delay, weak muscle tone (hypotonia), and reduced sensation in the limbs (peripheral neuropathy). Individuals with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome typically survive only into infancy or early childhood. MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is most frequently seen in the Navajo population of the southwestern United States. In this population, the condition is known as Navajo neurohepatopathy. People with Navajo neurohepatopathy tend to have a longer life expectancy than those with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. In addition to the signs and symptoms described above, people with Navajo neurohepatopathy may have problems with sensing pain that can lead to painless bone fractures and self-mutilation of the fingers or toes. Individuals with Navajo neurohepatopathy may lack feeling in the clear front covering of the eye (corneal anesthesia), which can lead to open sores and scarring on the cornea, resulting in impaired vision. The cause of these additional features is unknown. ## Frequency MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is thought to be a rare condition. Approximately 30 cases have been described in the scientific literature, including seven families with Navajo neurohepatopathy. Within the Navajo Nation of the southwestern United States, Navajo neurohepatopathy is estimated to occur in 1 in 1,600 newborns. ## Causes As the condition name suggests, mutations in the MPV17 gene cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. The protein produced from the MPV17 gene is located in the inner membrane of cell structures called mitochondria. Mitochondria are involved in a wide variety of cellular activities, including energy production, chemical signaling, and regulation of cell growth, division, and death. Mitochondria contain their own DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. It is likely that the MPV17 protein is involved in the maintenance of mtDNA. Having an adequate amount of mtDNA is essential for normal energy production within cells. MPV17 gene mutations that cause MPV17-related hepatocerebral mitochondrial DNA depletion syndrome lead to production of a protein with impaired function. One mutation causes all cases of Navajo neurohepatopathy and results in the production of an unstable MPV17 protein that is quickly broken down. A dysfunctional or absent MPV17 protein leads to problems with the maintenance of mtDNA, which can cause a reduction in the amount of mtDNA (known as mitochondrial DNA depletion). Mitochondrial DNA depletion impairs mitochondrial function in many of the body's cells and tissues, particularly the brain, liver, and other tissues that have high energy requirements. Reduced mitochondrial function in the liver and brain lead to the liver failure and neurological dysfunction associated with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. Researchers suggest that the less mtDNA that is available in cells, the more severe the features of Navajo neurohepatopathy. ### Learn more about the gene associated with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome * MPV17 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MPV17-related hepatocerebral mitochondrial DNA depletion syndrome

c1850407

medlineplus

https://medlineplus.gov/genetics/condition/mpv17-related-hepatocerebral-mitochondrial-dna-depletion-syndrome/

{"gard": ["3972"], "mesh": ["C538344"], "omim": ["256810"], "synonyms": []}

## Description Proteins of the SPRR family are components of the cornified cell envelope, which provides the protective barrier function of stratified squamous epithelial cells. However, SPRR2C contains a premature stop codon and appears to be a pseudogene (Gibbs et al., 1993; Cabral et al., 2001). Cloning and Expression Gibbs et al. (1993) reported that SPRR2C appears to be a pseudogene due to a C-to-T transition in the sixth codon, resulting in a TAG stop codon. By sequencing the SPRR gene cluster on chromosome 1, Cabral et al. (2001) identified SPRR2C, which contains a stop codon at codon 6. RT-PCR detected high SPRR2C expression in cervix, with lower expression in esophagus and cultured differentiated human keratinocytes. No SPRR2C expression was detected in uterus, ovary, skin, or undifferentiated keratinocytes. Gene Function Using RT-PCR, Cabral et al. (2001) found that ultraviolet C irradiation induced expression of SPRR2C in cultured human keratinocytes. Gene Structure Cabral et al. (2001) determined that SPRR2C, like all other SPRR2 genes, has 2 exons. Exon 1 is noncoding. Mapping Using long-distance PCR, Cabral et al. (2001) mapped the SPRR2C gene to an SPRR2 gene cluster spanning 100 kb of chromosome 1q21. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

SMALL PROLINE-RICH PROTEIN 2C, PSEUDOGENE

None

omim

https://www.omim.org/entry/182269

{"omim": ["182269"]}

Cerebellar stroke syndrome The three major arteries of the cerebellum: the SCA, AICA, and PICA SpecialtyNeurology Left sided cerebellar stroke due to occlusion of a vertebral artery Cerebellar stroke syndrome is a condition in which the circulation to the cerebellum is impaired due to a lesion of the superior cerebellar artery, anterior inferior cerebellar artery or the posterior inferior cerebellar artery.[1] Cardinal signs include vertigo, headache, vomiting, and ataxia.[2] Cerebellar strokes account for only 2-3% of the 600,000 strokes that occur each year in the United States.[3] They are far less common than strokes which occur in the cerebral hemispheres. In recent years mortality rates have decreased due to advancements in health care which include earlier diagnosis through MRI and CT scanning.[4] Advancements have also been made which allow earlier management for common complications of cerebellar stroke such as brainstem compression and hydrocephalus.[4] Research is still needed in the area of cerebellar stroke management; however, several factors may lead to poor outcomes in individuals who have a cerebellar stroke. These factors include: 1. Declining levels of consciousness 2. New signs of brainstem involvement 3. Progressing Hydrocephalus 4. Stroke to the midline of the cerebellum (a.k.a. the vermis) [4] ## References[edit] 1. ^ Urban, P.P.; Wicht, S.; Vukurevic, G.; Fitzek, C.; et al. (2001). "Dysarthria in acute ischemic stroke: Lesion topography, clinicoradiologic correlation, and etiology". Neurology. 56 (8): 1021–7. doi:10.1212/WNL.56.8.1021. PMID 11320172. 2. ^ Caplan, Louis R.; Bogousslavsky, Julien (2001). Stroke Syndromes. Cambridge University Press. ISBN 978-0521771429.[page needed] 3. ^ Kelly, P.J.; Stein, J.; Shafqat, S.; Eskey, C.; et al. (2001). "Functional recovery after rehabilitation for cerebellar stroke". Stroke. 32 (2): 530–4. doi:10.1161/01.STR.32.2.530. PMID 11157193. 4. ^ a b c Jensen, M.B.; St. Louis, E.K. (2005). "Management of acute cerebellar stroke". Archives of Neurology. 62 (4): 537–44. doi:10.1001/archneur.62.4.537. PMID 15824250. ## Further reading[edit] * Macdonell, R.A.; Kalnins, R.M.; Donnan, G.A. (1987). "Cerebellar infarction: Natural history, prognosis, and pathology". Stroke. 18 (5): 849–55. doi:10.1161/01.STR.18.5.849. PMID 3629642. * Edlow, J.A.; Newman-Toker, D.E.; Savitz, S.I. (2008). "Diagnosis and initial management of cerebellar infarction". The Lancet Neurology. 7 (10): 951–64. doi:10.1016/S1474-4422(08)70216-3. PMID 18848314. * Norrving, Bo (2014). Oxford Textbook of Stroke and Cerebrovascular Disease. Oxford University Press. pp. 90–1. ISBN 9780199641208. * Nowe, Tim; Jütter, Eric (2014). "Ch. 17: Critical Care of Cerebellar Stroke". In Schwab, Stefan; Hanley, Daniel; Mendelow, A. David (eds.). Critical Care of the Stroke Patient. Cambridge University Press. pp. 206–25. ISBN 9780521762564. * Manto, Mario Ubaldo (2010). "Ch. 8: Cerebellar Stroke". Cerebellar Disorders: A Practical Approach to Diagnosis and Management. Cambridge University Press. pp. 88–101. ISBN 9780521878135. ## External links[edit] Classification D * ICD-10: G46.4 * ICD-9-CM: 434.91 * Image of cerebellar stroke * Images of cerebellar stroke at MedPix * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar insufficiency * Subclavian steal syndrome Classification * Brain ischemia * Cerebral infarction * Classification * Transient ischemic attack * Total anterior circulation infarct * Partial anterior circulation infarct Other * CADASIL * Binswanger's disease * Transient global amnesia Haemorrhagic stroke Extra-axial * Epidural * Subdural * Subarachnoid Cerebral/Intra-axial * Intraventricular Brainstem * Duret haemorrhages General * Intracranial hemorrhage Aneurysm * Intracranial aneurysm * Charcot–Bouchard aneurysm Other * Cerebral vasculitis * Cerebral venous sinus thrombosis * v * t * e Symptoms, signs and syndromes associated with lesions of the brain and brainstem Brainstem Medulla (CN 8, 9, 10, 12) * Lateral medullary syndrome/Wallenberg * PICA * Medial medullary syndrome/Dejerine * ASA Pons (CN 5, 6, 7, 8) * Upper dorsal pontine syndrome/Raymond-Céstan syndrome * Lateral pontine syndrome (AICA) (lateral) * Medial pontine syndrome/Millard–Gubler syndrome/Foville's syndrome (basilar) * Locked-in syndrome * Internuclear ophthalmoplegia * One and a half syndrome Midbrain (CN 3, 4) * Weber's syndrome * ventral peduncle, PCA * Benedikt syndrome * ventral tegmentum, PCA * Parinaud's syndrome * dorsal, tumor * Claude's syndrome Other * Alternating hemiplegia Cerebellum * Latearl * Dysmetria * Dysdiadochokinesia * Intention tremor) * Medial * Cerebellar ataxia Basal ganglia * Chorea * Dystonia * Parkinson's disease Cortex * ACA syndrome * MCA syndrome * PCA syndrome * Frontal lobe * Expressive aphasia * Abulia * Parietal lobe * Receptive aphasia * Hemispatial neglect * Gerstmann syndrome * Astereognosis * Occipital lobe * Bálint's syndrome * Cortical blindness * Pure alexia * Temporal lobe * Cortical deafness * Prosopagnosia Thalamus * Thalamic syndrome Other * Upper motor neuron lesion * Aphasia *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Cerebellar stroke syndrome

c0451672

wikipedia

https://en.wikipedia.org/wiki/Cerebellar_stroke_syndrome

{"icd-9": ["434.91"], "icd-10": ["G46.4"], "wikidata": ["Q5064077"]}

A number sign (#) is used with this entry because the Russe type of hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease type 4G (CMT4G), is caused by homozygous mutation in the HK1 gene (142600) on chromosome 10q22. For a discussion of genetic heterogeneity of autosomal recessive hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease, see CMT4A (214400). Description HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy (summary by Sevilla et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease, see CMT4A (214400). Clinical Features During studies of Romany (Gypsy) families with the Lom type of hereditary motor and sensory neuropathy (CMT4D; 601455), Rogers et al. (2000) identified a large kindred with 2 independently segregating autosomal recessive neuropathies. The novel disorder, which the authors called 'hereditary motor and sensory neuropathy/Russe' (HMSNR), presented as a severe disabling form of Charcot-Marie-Tooth disease with prominent sensory loss, moderately reduced motor nerve conduction velocity, and a high threshold for electrical nerve stimulation. Thomas et al. (2001) reported 21 affected individuals from 10 families with HMSNR. Distal lower limb weakness began between ages 8 and 16 years, and upper limb involvement began between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in 2 instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was a loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. Navarro and Teijeira (2003) provided a detailed review of neuromuscular disorders among the Romani Gypsies. Sevilla et al. (2013) reported 11 patients from 7 unrelated Spanish Gypsy families with HMSNR. All except 1 developed distal lower limb weakness in the first decade; 1 had onset at age 16 years. Distal upper limb weakness was also present in all patients, but showed a slightly later and more variable onset. About half of patients later had proximal muscle involvement. All patients had distal sensory loss with areflexia and pes cavus, and 5 had scoliosis. The majority of patients walked with difficulty, 4 needed orthoses, and an older patient was wheelchair-bound. Neurophysiologic studies were mostly consistent with demyelination, although some were in the intermediate range. Sural nerve biopsy of 1 patient showed thin myelin sheath thickness and clusters of regenerative fibers. Mapping By genome scan in 2 branches of a large kindred with hereditary motor and sensory neuropathy, Rogers et al. (2000) detected linkage to the 10q22-q23 region containing the early growth response-2 gene (EGR2; 129010). By sequence analysis and the detection of an intragenic polymorphism, Rogers et al. (2000) excluded EGR2 as the site of mutation in HMSNR. By further linkage analysis and recombination mapping, the authors refined the position of HMSNR to a small interval on 10q23.2, flanked by markers telomeric to EGR2. In this interval, a conserved 7-marker haplotype was shared by all disease chromosomes, suggesting a single founder mutation. Claramunt et al. (2007) found that 3 of 20 Spanish Gypsy families with autosomal recessive demyelinating neuropathy had HMSN-Russe as indicated by positive linkage results to the 10q23 region. Molecular Genetics In all 34 individuals with Russe type of hereditary motor and sensory neuropathy who were studied, Hantke et al. (2009) identified 2 homozygous sequence changes in the HK1 gene (142600), which maps within the candidate disease interval on chromosome 10q. One was a G-to-C transversion at a highly conserved nucleotide in the putative AltT2 exon located in the 5-prime region upstream of HK1 (142600.0003), and the other was an intronic G-to-A transition downstream of the AltT2 change; the G-to-A transition was not highly conserved, and thus not thought to be pathogenic. These 2 variants were found in heterozygous state in 5 of 790 control individuals representing a cross-section of the Gypsy population, but not in 233 Bulgarian controls. AltT2-containing transcripts in the mouse peripheral nerve were rare compared to the coding region of HK1. However, 6 of 8 testis AltT2-containing isoforms were found, with expression patterns differing between the peripheral nerve and the brain and between newborn and adult tissues in mice. There was no difference in HK1 mRNA in Schwann cells derived from patients or controls, and patient cells showed no evidence of HK1 enzyme activity compared to controls. Bioinformatic tools did not suggest an effect of the G-C change on HK1 gene splicing or binding sites for interacting proteins. However, there was evidence that the G-C change may cause a ter-to-tyr substitution in 1 upstream open reading frame that had a non-AUG start codon, which could potentially disrupt HK1 translation regulation. Hantke et al. (2009) speculated that non-OMM-binding HK1 may play a role in the pathogenesis of HMSNR. Sevilla et al. (2013) found that 11 patients from 9 Roma Gypsy families were homozygous for the HK1 variant (g.9712G-C; 142600.0003) identified by Hantke et al. (2009), and haplotype analysis confirmed a founder effect in this population. Population Genetics HMSNR is the second most common cause of Charcot-Marie-Tooth disease in the Spanish Gypsy population (Roma) after CMT4C (601596), and is associated with a homozygous founder variant in the HK1 gene (142600.0003). Sevilla et al., 2013 found that 11 patients from 9 Roma Gypsy families with the disorder were homozygous for the HK1 variant, and haplotype analysis indicated a founder effect. The founding ancestor was estimated to have lived at the end of the 18th century, when a population split occurred from a tribal group and the Gypsy population in Spain increased under the rule of Charles III. Nomenclature De Sandre-Giovannoli et al. (2005) suggested that HMSNR be referred to as Charcot-Marie-Tooth disease type 4G (CMT4G). INHERITANCE \- Autosomal recessive SKELETAL Spine \- Scoliosis (in some patients) Hands \- Hand deformity Feet \- Foot deformity MUSCLE, SOFT TISSUES \- Distal muscle weakness \- Proximal lower limb muscle weakness, later (in some patients) NEUROLOGIC Peripheral Nervous System \- Prominent sensory loss, distal \- Distal limb weakness \- Distal limb paralysis \- Difficulty walking \- Hyporeflexia \- Reduced motor nerve conduction velocity \- Increased threshold for electrical stimulation \- Loss of larger myelinated nerve fibers \- Thin myelin sheaths \- Regenerative activity on nerve biopsy \- Hypomyelination on nerve biopsy \- Reduced nerve conduction velocities (demyelinating range) MISCELLANEOUS \- Age of onset of distal lower limb weakness 8-16 years \- Age of onset of upper limb involvement 10-43 years \- Progressive disorder \- Described in individuals of Roma Gypsy origin (founder mutation) MOLECULAR BASIS \- Caused by mutation in the hexokinase-1 gene (HK1, 142600.0003 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

NEUROPATHY, HEREDITARY MOTOR AND SENSORY, RUSSE TYPE

c1854449

omim

https://www.omim.org/entry/605285

{"doid": ["0110196"], "mesh": ["C535813"], "omim": ["605285"], "orphanet": ["99953"], "synonyms": ["Alternative titles", "CHARCOT-MARIE-TOOTH DISEASE, TYPE 4G", "CHARCOT-MARIE-TOOTH DISEASE, AUTOSOMAL RECESSIVE, TYPE 4G", "HEREDITARY MOTOR AND SENSORY NEUROPATHY, RUSSE TYPE", "CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 4G"]}

This article relies largely or entirely on a single source. Relevant discussion may be found on the talk page. Please help improve this article by introducing citations to additional sources. Find sources: "Infantile acne" – news · newspapers · books · scholar · JSTOR (November 2020) Infantile acne SpecialtyDermatology Infantile acne is a cutaneous condition that usually presents between 3 to 6 months of age.[1]:500 ## See also[edit] * List of cutaneous conditions * Neonatal acne ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: L70.4 (ILDS L70.400) * v * t * e Disorders of skin appendages Nail * thickness: Onychogryphosis * Onychauxis * color: Beau's lines * Yellow nail syndrome * Leukonychia * Azure lunula * shape: Koilonychia * Nail clubbing * behavior: Onychotillomania * Onychophagia * other: Ingrown nail * Anonychia * ungrouped: Paronychia * Acute * Chronic * Chevron nail * Congenital onychodysplasia of the index fingers * Green nails * Half and half nails * Hangnail * Hapalonychia * Hook nail * Ingrown nail * Lichen planus of the nails * Longitudinal erythronychia * Malalignment of the nail plate * Median nail dystrophy * Mees' lines * Melanonychia * Muehrcke's lines * Nail–patella syndrome * Onychoatrophy * Onycholysis * Onychomadesis * Onychomatricoma * Onychomycosis * Onychophosis * Onychoptosis defluvium * Onychorrhexis * Onychoschizia * Platonychia * Pincer nails * Plummer's nail * Psoriatic nails * Pterygium inversum unguis * Pterygium unguis * Purpura of the nail bed * Racquet nail * Red lunulae * Shell nail syndrome * Splinter hemorrhage * Spotted lunulae * Staining of the nail plate * Stippled nails * Subungual hematoma * Terry's nails * Twenty-nail dystrophy Hair Hair loss/ Baldness * noncicatricial alopecia: Alopecia * areata * totalis * universalis * Ophiasis * Androgenic alopecia (male-pattern baldness) * Hypotrichosis * Telogen effluvium * Traction alopecia * Lichen planopilaris * Trichorrhexis nodosa * Alopecia neoplastica * Anagen effluvium * Alopecia mucinosa * cicatricial alopecia: Pseudopelade of Brocq * Central centrifugal cicatricial alopecia * Pressure alopecia * Traumatic alopecia * Tumor alopecia * Hot comb alopecia * Perifolliculitis capitis abscedens et suffodiens * Graham-Little syndrome * Folliculitis decalvans * ungrouped: Triangular alopecia * Frontal fibrosing alopecia * Marie Unna hereditary hypotrichosis Hypertrichosis * Hirsutism * Acquired * localised * generalised * patterned * Congenital * generalised * localised * X-linked * Prepubertal Acneiform eruption Acne * Acne vulgaris * Acne conglobata * Acne miliaris necrotica * Tropical acne * Infantile acne/Neonatal acne * Excoriated acne * Acne fulminans * Acne medicamentosa (e.g., steroid acne) * Halogen acne * Iododerma * Bromoderma * Chloracne * Oil acne * Tar acne * Acne cosmetica * Occupational acne * Acne aestivalis * Acne keloidalis nuchae * Acne mechanica * Acne with facial edema * Pomade acne * Acne necrotica * Blackhead * Lupus miliaris disseminatus faciei Rosacea * Perioral dermatitis * Granulomatous perioral dermatitis * Phymatous rosacea * Rhinophyma * Blepharophyma * Gnathophyma * Metophyma * Otophyma * Papulopustular rosacea * Lupoid rosacea * Erythrotelangiectatic rosacea * Glandular rosacea * Gram-negative rosacea * Steroid rosacea * Ocular rosacea * Persistent edema of rosacea * Rosacea conglobata * variants * Periorificial dermatitis * Pyoderma faciale Ungrouped * Granulomatous facial dermatitis * Idiopathic facial aseptic granuloma * Periorbital dermatitis * SAPHO syndrome Follicular cysts * "Sebaceous cyst" * Epidermoid cyst * Trichilemmal cyst * Steatocystoma * simplex * multiplex * Milia Inflammation * Folliculitis * Folliculitis nares perforans * Tufted folliculitis * Pseudofolliculitis barbae * Hidradenitis * Hidradenitis suppurativa * Recurrent palmoplantar hidradenitis * Neutrophilic eccrine hidradenitis Ungrouped * Acrokeratosis paraneoplastica of Bazex * Acroosteolysis * Bubble hair deformity * Disseminate and recurrent infundibulofolliculitis * Erosive pustular dermatitis of the scalp * Erythromelanosis follicularis faciei et colli * Hair casts * Hair follicle nevus * Intermittent hair–follicle dystrophy * Keratosis pilaris atropicans * Kinking hair * Koenen's tumor * Lichen planopilaris * Lichen spinulosus * Loose anagen syndrome * Menkes kinky hair syndrome * Monilethrix * Parakeratosis pustulosa * Pili (Pili annulati * Pili bifurcati * Pili multigemini * Pili pseudoannulati * Pili torti) * Pityriasis amiantacea * Plica neuropathica * Poliosis * Rubinstein–Taybi syndrome * Setleis syndrome * Traumatic anserine folliculosis * Trichomegaly * Trichomycosis axillaris * Trichorrhexis (Trichorrhexis invaginata * Trichorrhexis nodosa) * Trichostasis spinulosa * Uncombable hair syndrome * Wooly hair nevus Sweat glands Eccrine * Miliaria * Colloid milium * Miliaria crystalline * Miliaria profunda * Miliaria pustulosa * Miliaria rubra * Occlusion miliaria * Postmiliarial hypohidrosis * Granulosis rubra nasi * Ross’ syndrome * Anhidrosis * Hyperhidrosis * Generalized * Gustatory * Palmoplantar Apocrine * Body odor * Chromhidrosis * Fox–Fordyce disease Sebaceous * Sebaceous hyperplasia This cutaneous condition article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Infantile acne

c0263437

wikipedia

https://en.wikipedia.org/wiki/Infantile_acne

{"icd-10": ["L70.4"], "wikidata": ["Q341991"]}

Prothrombin deficiency is a bleeding disorder that slows the blood clotting process. People with this condition often experience prolonged bleeding following an injury, surgery, or having a tooth pulled. In severe cases of prothrombin deficiency, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Women with prothrombin deficiency can have prolonged and sometimes abnormally heavy menstrual bleeding. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of prothrombin deficiency do not involve spontaneous bleeding, and the condition may only become apparent following surgery or a serious injury. ## Frequency Prothrombin deficiency is very rare; it is estimated to affect 1 in 2 million people in the general population. ## Causes Mutations in the F2 gene cause prothrombin deficiency. The F2 gene provides instructions for making the prothrombin protein (also called coagulation factor II), which plays a critical role in the formation of blood clots in response to injury. Prothrombin is the precursor to thrombin, a protein that initiates a series of chemical reactions to form a blood clot. After an injury, clots protect the body by sealing off damaged blood vessels and preventing further blood loss. F2 gene mutations reduce the production of prothrombin in cells, which prevents clots from forming properly in response to injury. Problems with blood clotting can lead to excessive bleeding. Some mutations drastically reduce the activity of prothrombin and can lead to severe bleeding episodes. Other F2 gene mutations allow for a moderate amount of prothrombin activity, typically resulting in mild bleeding episodes. ### Learn more about the gene associated with Prothrombin deficiency * F2 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Prothrombin deficiency

c0272317

medlineplus

https://medlineplus.gov/genetics/condition/prothrombin-deficiency/

{"gard": ["2926"], "mesh": ["C562724"], "omim": ["613679"], "synonyms": []}

Human viral disease Rift Valley fever TEM micrograph of tissue infected with Rift Valley fever virus SpecialtyInfectious disease SymptomsFever, muscle pains, headaches[1] ComplicationsLoss of sight, confusion, bleeding, liver problems[1] DurationUp to a week[1] CausesPhlebovirus spread by an infected animal or mosquito[1] Diagnostic methodFinding antibodies or the virus in the blood[1] PreventionVaccinating animals against the disease, decreasing mosquito bites[1] TreatmentSupportive care[1] FrequencyOutbreaks in Africa and Arabia[1] Rift Valley fever (RVF) is a viral disease of humans and livestock that can cause mild to severe symptoms.[1] The mild symptoms may include: fever, muscle pains, and headaches which often last for up to a week.[1] The severe symptoms may include: loss of sight beginning three weeks after the infection, infections of the brain causing severe headaches and confusion, and bleeding together with liver problems which may occur within the first few days.[1] Those who have bleeding have a chance of death as high as 50%.[1] The disease is caused by the RVF virus, which is of the Phlebovirus type.[1] It is spread by either touching infected animal blood, breathing in the air around an infected animal being butchered, drinking raw milk from an infected animal, or the bite of infected mosquitoes.[1] Animals such as cows, sheep, goats, and camels may be affected.[1] In these animals it is spread mostly by mosquitoes.[1] It does not appear that one person can infect another person.[1] The disease is diagnosed by finding antibodies against the virus or the virus itself in the blood.[1] Prevention of the disease in humans is accomplished by vaccinating animals against the disease.[1] This must be done before an outbreak occurs because if it is done during an outbreak it may worsen the situation.[1] Stopping the movement of animals during an outbreak may also be useful, as may decreasing mosquito numbers and avoiding their bites.[1] There is a human vaccine; however, as of 2010 it is not widely available.[1] There is no specific treatment and medical efforts are supportive.[1] Outbreaks of the disease have only occurred in Africa and Arabia.[1] Outbreaks usually occur during periods of increased rain which increase the number of mosquitoes.[1] The disease was first reported among livestock in Rift Valley of Kenya in the early 1900s,[2] and the virus was first isolated in 1931.[1] ## Contents * 1 Signs and symptoms * 2 Cause * 2.1 Virology * 2.2 Transmission * 3 Pathogenesis * 4 Diagnosis * 5 Prevention * 6 Epidemiology * 7 Biological weapon * 8 Research * 9 See also * 10 References * 11 External links ## Signs and symptoms[edit] In humans, the virus can cause several syndromes. Usually, sufferers have either no symptoms or only a mild illness with fever, headache, muscle pains, and liver abnormalities. In a small percentage of cases (< 2%), the illness can progress to hemorrhagic fever syndrome, meningoencephalitis (inflammation of the brain and tissues lining the brain), or affect the eye. Patients who become ill usually experience fever, generalised weakness, back pain, dizziness, and weight loss at the onset of the illness. Typically, people recover within two to seven days after onset. About 1% of people with the disease die of it. In livestock, the fatality level is significantly higher. Pregnant livestock infected with RVF abort virtually 100% of foetuses. An epizootic (animal disease epidemic) of RVF is usually first indicated by a wave of unexplained abortions.[citation needed] Other signs in livestock include vomiting and diarrhoea, respiratory disease, fever, lethargy, anorexia and sudden death in young animals.[3] ## Cause[edit] ### Virology[edit] Rift Valley fever phlebovirus Phlebovirus virion and genome Virus classification (unranked): Virus Realm: Riboviria Kingdom: Orthornavirae Phylum: Negarnaviricota Class: Ellioviricetes Order: Bunyavirales Family: Phenuiviridae Genus: Phlebovirus Species: Rift Valley fever phlebovirus The virus belongs to the Bunyavirales order. This is an order of enveloped negative single stranded RNA viruses. All Bunyaviruses have an outer lipid envelope with two glycoproteins—G(N) and G(C)—required for cell entry. They deliver their genome into the host-cell cytoplasm by fusing their envelope with an endosomal membrane.[citation needed] The virus' G(C) protein has a class II membrane fusion protein architecture similar to that found in flaviviruses and alphaviruses.[4] This structural similarity suggests that there may be a common origin for these viral families. The virus' 11.5 kb tripartite genome is composed of single-stranded RNA. As a Phlebovirus, it has an ambisense genome. Its L and M segments are negative-sense, but its S segment is ambisense.[5] These three genome segments code for six major proteins: L protein (viral polymerase), the two glycoproteins G(N) and G(C), the nucleocapsid N protein, and the nonstructural NSs and NSm proteins. ### Transmission[edit] See also: Prevention of viral hemorrhagic fever The virus is transmitted through mosquito vectors, as well as through contact with the tissue of infected animals. Two species—Culex tritaeniorhynchus and Aedes vexans—are known to transmit the virus.[6] Other potential vectors include Aedes caspius, Aedes mcintosh, Aedes ochraceus, Culex pipiens, Culex antennatus, Culex perexiguus, Culex zombaensis and Culex quinquefasciatus.[7][8][9] Contact with infected tissue is considered to be the main source of human infections.[10] The virus has been isolated from two bat species: the Peter's epauletted fruit bat (Micropteropus pusillus) and the aba roundleaf bat (Hipposideros abae), which are believed to be reservoirs for the virus.[11] ## Pathogenesis[edit] Although many components of the RVFV's RNA play an important role in the virus’ pathology, the nonstructural protein encoded on the S segment (NSs) is the only component that has been found to directly affect the host. NSs is hostile and combative against the hosts interferon (IFNs) antiviral response.[12] IFNs are essential in order for the immune system to fight off viral infections in a host.[13] This inhibitory mechanism is believed to be due to a number of reasons, the first being, competitive inhibition of the formation of the transcription factor.[12] On this transcription factor, NSs interacts with and binds to a subunit that is needed for RNA polymerase I and II.[12][14] This interaction cause competitive inhibition with another transcription factor component and prevents the assembly process of the transcription factor complex, which results in the suppression of the host antiviral response.[12][14] Transcription suppression is believed to be another mechanism of this inhibitory process.[12] This occurs when an area of NSs interacts with and binds to the host's protein, SAP30 and forms a complex.[12][14] This complex causes histone acetylation to regress, which is needed for transcriptional activation of the IFN promoter.[14] This causes IFN expression to be obstructed. Lastly, NSs has also been known to affect regular activity of double-stranded RNA-dependent protein kinase R.. This protein is involved in cellular antiviral responses in the host. When RVFV is able to enter the hosts DNA, NSs forms a filamentous structure in the nucleus. This allows the virus to interact with specific areas of the hosts DNA that relates to segregation defects and induction of chromosome continuity. This increases host infectivity and decreases the host's antiviral response.[12] ## Diagnosis[edit] Diagnosis relies on viral isolation from tissues, or serological testing with an ELISA.[3] Other methods of diagnosis include Nucleic Acid Testing (NAT), cell culture, and IgM antibody assays.[15] As of September 2016, the Kenya Medical Research Institute (KEMRI) has developed a product called Immunoline, designed to diagnose the disease in humans much faster than in previous methods.[16] ## Prevention[edit] A person's chances of becoming infected can be reduced by taking measures to decrease contact with blood, body fluids, or tissues of infected animals and protection against mosquitoes and other bloodsucking insects. Use of mosquito repellents and bed nets are two effective methods. For persons working with animals in RVF-endemic areas, wearing protective equipment to avoid any exposure to blood or tissues of animals that may potentially be infected is an important protective measure.[17] Potentially, establishing environmental monitoring and case surveillance systems may aid in the prediction and control of future RVF outbreaks.[17] No vaccines are currently available for humans.[17][1] While a vaccines have been developed for humans, it has only been used experimentally for scientific personnel in high-risk environments.[1] Trials of a number of vaccines, such as NDBR-103 and TSI-GSD 200, are ongoing.[18] Different types of vaccines for veterinary use are available. The killed vaccines are not practical in routine animal field vaccination because of the need of multiple injections. Live vaccines require a single injection but are known to cause birth defects and abortions in sheep and induce only low-level protection in cattle. The live-attenuated vaccine, MP-12, has demonstrated promising results in laboratory trials in domesticated animals, but more research is needed before the vaccine can be used in the field. The live-attenuated clone 13 vaccine was recently registered and used in South Africa. Alternative vaccines using molecular recombinant constructs are in development and show promising results.[17] A vaccine has been conditionally approved for use in animals in the US.[19] It has been shown that knockout of the NSs and NSm nonstructural proteins of this virus produces an effective vaccine in sheep as well.[20] ## Epidemiology[edit] Distribution of Rift Valley fever in Africa: Blue, countries with endemic disease and substantial outbreaks of RVF; green, countries known to have some cases, periodic isolation of virus, or serologic evidence of RVF See also: List of Rift Valley fever outbreaks RVF outbreaks occur across sub-Saharan Africa, with outbreaks occurring elsewhere infrequently. Outbreaks of this disease usually correspond with the warm phases of the EI Niño/Southern Oscillation. During this time there is an increase in rainfall, flooding and greenness of vegetation index, which leads to an increase in mosquito vectors.[21] RVFV can be transmitted vertically in mosquitos, meaning that the virus can be passed from the mother to her offspring. During dry conditions, the virus can remain viable for a number of years in the egg. Mosquitos lay their eggs in water, where they eventually hatch. As water is essential for mosquito eggs to hatch, rainfall and flooding cause an increase in the mosquito population and an increased potential for the virus.[22] In Egypt in 1977–78, an estimated 200,000 people were infected and there were at least 594 deaths.[23][24] In Kenya in 1998, the virus killed more than 400 people. In September 2000, an outbreak was confirmed in Saudi Arabia and Yemen. On 19 October 2011, a case of Rift Valley fever contracted in Zimbabwe was reported in a Caucasian female traveler who returned to France after a 26-day stay in Marondera, Mashonaland East Province during July and August, 2011[25] but later classified as "not confirmed."[26] In 2006-2007, there was an outbreak in East Africa.[27] In 2007, there was an outbreak in Sudan.[28] In 2010, there was an outbreak in South Africa.[29][30] In 2016, there was an outbreak in Uganda.[31] In 2018, there was an outbreak in Kenya.[32] In 2018-2019, there was an outbreak in Mayotte.[33] ## Biological weapon[edit] Rift Valley fever was one of more than a dozen agents that the United States researched as potential biological weapons before the nation suspended its biological weapons program in 1969.[34][35] ## Research[edit] The disease is one of several identified by WHO as a likely cause of a future epidemic in a new plan developed after the Ebola epidemic for urgent research and development toward new diagnostic tests, vaccines and medicines.[36][37] ## See also[edit] * Viruses portal * Coalition for Epidemic Preparedness Innovations ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab "Rift Valley fever". Fact sheet N°207. World Health Organization. May 2010. Archived from the original on 15 April 2014. Retrieved 21 March 2014. 2. ^ Palmer SR (2011). Oxford textbook of zoonoses : biology, clinical practice, and public health control (2nd ed.). Oxford u.a.: Oxford Univ. Press. p. 423. ISBN 9780198570028. Archived from the original on 2017-09-08. 3. ^ a b Rift Valley Fever Archived 2012-05-08 at the Wayback Machine reviewed and published by WikiVet, accessed 12 October 2011. 4. ^ Dessau M, Modis Y (January 2013). "Crystal structure of glycoprotein C from Rift Valley fever virus". Proceedings of the National Academy of Sciences of the United States of America. 110 (5): 1696–701. Bibcode:2013PNAS..110.1696D. doi:10.1073/pnas.1217780110. PMC 3562824. PMID 23319635. 5. ^ "ViralZone: Phlebovirus". viralzone.expasy.org. Archived from the original on 2016-10-03. Retrieved 2016-09-14. 6. ^ Jupp PG, Kemp A, Grobbelaar A, Lema P, Burt FJ, Alahmed AM, Al Mujalli D, Al Khamees M, Swanepoel R (September 2002). "The 2000 epidemic of Rift Valley fever in Saudi Arabia: mosquito vector studies". Medical and Veterinary Entomology. 16 (3): 245–52. doi:10.1046/j.1365-2915.2002.00371.x. PMID 12243225. 7. ^ Turell MJ, Presley SM, Gad AM, Cope SE, Dohm DJ, Morrill JC, Arthur RR (February 1996). "Vector competence of Egyptian mosquitoes for Rift Valley fever virus". The American Journal of Tropical Medicine and Hygiene. 54 (2): 136–9. doi:10.4269/ajtmh.1996.54.136. PMID 8619436. 8. ^ Turell MJ, Lee JS, Richardson JH, Sang RC, Kioko EN, Agawo MO, Pecor J, O'Guinn ML (December 2007). "Vector competence of Kenyan Culex zombaensis and Culex quinquefasciatus mosquitoes for Rift Valley fever virus". Journal of the American Mosquito Control Association. 23 (4): 378–82. doi:10.2987/5645.1. PMID 18240513. S2CID 36591701. 9. ^ Fontenille D, Traore-Lamizana M, Diallo M, Thonnon J, Digoutte JP, Zeller HG (1998). "New vectors of Rift Valley fever in West Africa". Emerging Infectious Diseases. 4 (2): 289–93. doi:10.3201/eid0402.980218. PMC 2640145. PMID 9621201. 10. ^ Swanepoel R, Coetzer JA (2004). "Rift Valley fever". In Coetzer JA, Tustin RC (eds.). Infectious diseases of livestock (2nd ed.). Cape Town: Oxford University Press Southern Africa. pp. 1037–70. ISBN 978-0195761702. 11. ^ Boiro I, Konstaninov OK, Numerov AD (1987). "[Isolation of Rift Valley fever virus from bats in the Republic of Guinea]". Bulletin de la Société de Pathologie Exotique et de Ses Filiales (in French). 80 (1): 62–7. PMID 3607999. 12. ^ a b c d e f g Boshra H, Lorenzo G, Busquets N, Brun A (July 2011). "Rift valley fever: recent insights into pathogenesis and prevention". Journal of Virology. 85 (13): 6098–105. doi:10.1128/JVI.02641-10. PMC 3126526. PMID 21450816. 13. ^ Fensterl V, Sen GC (2009-01-01). "Interferons and viral infections". BioFactors. 35 (1): 14–20. doi:10.1002/biof.6. PMID 19319841. S2CID 27209861. 14. ^ a b c d Ikegami T, Makino S (May 2011). "The pathogenesis of Rift Valley fever". Viruses. 3 (5): 493–519. doi:10.3390/v3050493. PMC 3111045. PMID 21666766. 15. ^ Fields BN, Knipe DM, Howley PM (2013). Fields Virology, 6th Edition. Philadelphia, PA, USA: Wolters Kluwer, Lippincott Williams & Wilkins. p. 441. ISBN 978-1-4511-0563-6. 16. ^ "Kemri develops kit for rapid test of viral disease". Archived from the original on 2016-09-06. Retrieved 2016-09-14. 17. ^ a b c d "Prevention: Rift Valley Fever | CDC". US Centers for Disease Control and Prevention. Retrieved 24 September 2018. This article incorporates text from this source, which is in the public domain. 18. ^ Fawzy M, Helmy YA (February 2019). "The One Health Approach is Necessary for the Control of Rift Valley Fever Infections in Egypt: A Comprehensive Review". Viruses. 11 (2): 139. doi:10.3390/v11020139. PMC 6410127. PMID 30736362. 19. ^ Ikegami T, Hill TE, Smith JK, Zhang L, Juelich TL, Gong B, Slack OA, Ly HJ, Lokugamage N, Freiberg AN (July 2015). "Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments". Journal of Virology. 89 (14): 7262–76. doi:10.1128/JVI.00135-15. PMC 4473576. PMID 25948740. 20. ^ Bird BH, Maartens LH, Campbell S, Erasmus BJ, Erickson BR, Dodd KA, Spiropoulou CF, Cannon D, Drew CP, Knust B, McElroy AK, Khristova ML, Albariño CG, Nichol ST (December 2011). "Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep". Journal of Virology. 85 (24): 12901–9. doi:10.1128/JVI.06046-11. PMC 3233145. PMID 21976656. 21. ^ Nanyingi MO, Munyua P, Kiama SG, Muchemi GM, Thumbi SM, Bitek AO, Bett B, Muriithi RM, Njenga MK (2015-07-31). "A systematic review of Rift Valley Fever epidemiology 1931-2014". Infection Ecology & Epidemiology. 5: 28024. doi:10.3402/iee.v5.28024. PMC 4522434. PMID 26234531. Archived from the original on 2016-12-02. 22. ^ "Rift Valley Fever | CDC". www.cdc.gov. Archived from the original on 2016-12-04. Retrieved 2016-12-01. 23. ^ Arzt J, White WR, Thomsen BV, Brown CC (January 2010). "Agricultural diseases on the move early in the third millennium". Veterinary Pathology. 47 (1): 15–27. doi:10.1177/0300985809354350. PMID 20080480. S2CID 31753926. 24. ^ Bird BH, Ksiazek TG, Nichol ST, Maclachlan NJ (April 2009). "Rift Valley fever virus". Journal of the American Veterinary Medical Association. 234 (7): 883–93. doi:10.2460/javma.234.7.883. PMID 19335238. S2CID 16239209. 25. ^ Vesin G (19 October 2011). "Rift Valley Fever, human—France: ex Zimbabwe (Mashonaland East) first report". ProMED mail. International Society for Infectious Diseases. 20111020.3132. Archived from the original on 18 January 2015. 26. ^ Grandadam M, Malvy D (29 November 2011). "Rift Valley Fever, human—France: ex Zimbabwe (Mashonaland East) not". ProMED mail. International Society for Infectious Diseases. 20111129.3486. Archived from the original on 18 January 2015. 27. ^ "At least 75 people die of Rift Valley Fever in Kenya". International Herald Tribune. 7 January 2007. Archived from the original on 9 January 2007. 28. ^ "Deadly fever spreads Kenya Panic". BBC. 26 January 2007. Archived from the original on 1 May 2008. 29. ^ ProMED-mail Archived 2011-07-28 at the Wayback Machine. ProMED-mail. Retrieved on 2014-05-12. 30. ^ "Rift Valley fever in South Africa". WHO. Archived from the original on 2010-04-12. 31. ^ "Outbreak Summaries | Rift Valley Fever | CDC". 2019-02-15. 32. ^ "Rift Valley fever – Kenya". WHO. 18 June 2018. Retrieved 1 July 2018. 33. ^ "Rift Valley Fever – Mayotte (France)". WHO. 13 May 2019. Retrieved 15 May 2019. 34. ^ "Chemical and Biological Weapons: Possession and Programs Past and Present", James Martin Center for Nonproliferation Studies, Middlebury College, April 9, 2002, accessed November 14, 2008. 35. ^ "Select Agents and Toxins" (PDF). USDA-APHIS and CDC: National Select Agent Registry. 2011-09-19. Archived from the original (PDF) on 2012-02-25. 36. ^ Kieny M. "After Ebola, a Blueprint Emerges to Jump-Start R&D". Scientific American Blog Network. Archived from the original on 20 December 2016. Retrieved 13 December 2016. 37. ^ "LIST OF PATHOGENS". World Health Organization. Archived from the original on 20 December 2016. Retrieved 13 December 2016. ## External links[edit] * CDC RVF Information Page * Rift Valley Fever disease card at OIE * "Rift Valley fever". Fact sheet N°207. World Health Organization. May 2010. Retrieved 21 March 2014. * "Rift Valley fever virus". NCBI Taxonomy Browser. 11588. Classification D * ICD-10: A92.4 * ICD-9-CM: 066.3 * MeSH: D012295 * DiseasesDB: 31094 External resources * Orphanet: 319251 * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox Taxon identifiers * Wikidata: Q14276794 * Wikispecies: Rift Valley fever phlebovirus * IRMNG: 11460687 * ISC: 66184 * NCBI: 11588 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Rift Valley fever

c0035613

wikipedia

https://en.wikipedia.org/wiki/Rift_Valley_fever

{"mesh": ["D012295"], "umls": ["C0035613"], "icd-9": ["066.3"], "orphanet": ["319251"], "wikidata": ["Q326638"]}

## Clinical Features Abou Jamra et al. (2011) reported a consanguineous Syrian family (MR019) in which 4 individuals had nonsyndromic mental retardation. Symptoms included mild motor delay, moderate intellectual disability, and single word speech. Three patients had early-onset epilepsy. Mapping Najmabadi et al. (2007) reported a large consanguineous Iranian family (M010) in which 5 individuals had nonsyndromic moderate mental retardation. Linkage analysis identified a candidate locus spanning the pericentromeric region on chromosome 16, termed MRT10, with a maximum lod score of 5.2. Haplotype analysis delineated a 26.25-Mb candidate region between SNPs rs724466 and rs3901517. By homozygosity mapping of a consanguineous Syrian family with mental retardation, Abou Jamra et al. (2011) found linkage to a 21.7-Mb region in the pericentromeric region of chromosome 16 between SNPs rs7197568 and rs7197227 (lod score of 3.91). Abou Jamra et al. (2011) referred to this locus as 'MRT20.' INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Intellectual disability, moderate \- Motor delay, mild \- Can speak single words \- Epilepsy, early onset (in some patients) MISCELLANEOUS \- Based on a report of 1 consanguineous Syrian family (last curated November 2011) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MENTAL RETARDATION, AUTOSOMAL RECESSIVE 10

c1970194

omim

https://www.omim.org/entry/611096

{"doid": ["0060308"], "mesh": ["C567013"], "omim": ["611096"], "orphanet": ["88616"], "synonyms": ["MENTAL RETARDATION, AUTOSOMAL RECESSIVE 20", "Alternative titles", "NS-ARID", "AR-NSID"]}

Trigeminal neuralgia is a nerve disorder that causes a stabbing or electric-shock-like pain in parts of the face. The pain lasts a few seconds to a few minutes, and usually on only one side of the face. It can also cause muscle spasms in the face the same time as the pain. The pain may result from a blood vessel pressing against the trigeminal nerve (the nerve that carries pain, feeling, and other sensations from the brain to the skin of the face), as a complication of multiple sclerosis, or due to compression of the nerve by a tumor or cyst. In some cases, the cause is unknown. Treatment options include medicines, surgery, and complementary approaches. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Trigeminal neuralgia

c0040997

gard

https://rarediseases.info.nih.gov/diseases/7805/trigeminal-neuralgia

{"mesh": ["D014277"], "omim": ["190400"], "umls": ["C0040997"], "orphanet": ["221091"], "synonyms": ["Tic Douloureux"]}

Mouse egasyn, a 64-kD luminal endoplasmic reticulum (ER) glycoprotein, has dual functions. In tissues such as the liver, kidney, and submandibular gland, binding by egasyn sequesters beta-glucuronidase in the ER. Also, egasyn is identical to esterase-22, one of a family of mouse carboxylesterases with broad specificities. Ovnic et al. (1991) used the polymerase chain reaction (PCR) for the isolation of murine egasyn cDNAs. At least 9 nonspecific carboxylesterases are encoded by genes located in 2 clusters in the esterase region on mouse chromosome 8 (Peters, 1982). Medda et al. (1986) mapped egasyn to cluster 1, which includes esterase-1, esterase-6, and esterase-9. Ovnic et al. (1991) confirmed the mapping of the Es22 gene to cluster 1 on mouse chromosome 8. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

EGASYN

None

omim

https://www.omim.org/entry/129905

{"omim": ["129905"], "synonyms": ["Alternative titles", "ESTERASE 22"]}

Acatalasia Other namesAcatalasemia, or Takahara's disease[1]:809 Basic structure of a peroxisome SpecialtyEndocrinology Acatalasia is an autosomal recessive peroxisomal disorder caused by absent or very low levels of the enzyme catalase.[2] Catalase breaks down hydrogen peroxide in cells into water and oxygen. Low levels of catalase can cause hydrogen peroxide to build up, causing damage to cells. ## Contents * 1 Presentation * 2 Genetic * 3 Diagnosis * 4 Management * 5 Epidemiology * 6 History * 7 See also * 8 References * 9 External links ## Presentation[edit] The disorder is relatively benign, although it causes an increased incidence of oral ulcers, and can under rare circumstances lead to gangrene.[3][2] Symptoms primary affect children.[4] ## Genetic[edit] Acatalasia is often the result of mutations in both copies of the CAT gene which codes for the enzyme catalase.[5] There are multiple types of mutation that can cause this condition. Inheriting a single CAT mutation results in hypocatalasia, in which catalase levels are reduced, but still at functional levels.[6] ## Diagnosis[edit] This disorder is commonly diagnosed pouring hydrogen peroxide on the patient's blood sample. Instead of a very bubbling reaction, blood turns brown-colored, which means the patient suffers from acatalasia ## Management[edit] This section is empty. You can help by adding to it. (April 2017) ## Epidemiology[edit] In parts of Japan, this condition has been found in approximately 1.4% of people.[4] Researchers estimate that the condition occurs in 1 in 20,000 people in Hungary and Switzerland.[5] ## History[edit] In 1948, Dr. Shigeo Takahara (1908–1994), a Japanese otolaryngologist first reported this new disease.[7] He had examined a patient with an oral ulcer. He had spread hydrogen peroxide on the diseased part, but oxygen was not generated due to the lack of catalase. ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 2. ^ a b Reference, Genetics Home. "acatalasemia". Genetics Home Reference. Retrieved 7 November 2017. 3. ^ Takahara, Shigeo; Hamilton, H. B.; Neel, J. V.; Kobara, T. Y.; Ogura, Y.; Nishimura, E. T. (1960). "Hypocatalasemia: a new genetic carrier state". Journal of Clinical Investigation. 39 (4): 610–619. doi:10.1172/JCI104075. PMC 293346. PMID 13836629. 4. ^ a b Bissonnette, Bruno; Luginbuehl, Igor; Marciniak, Bruno; Dalens, Bernard J. (2006). Acatalasia/Acatalasemia. Syndromes: Rapid Recognition and Perioperative Implications. The McGraw-Hill Companies. 5. ^ a b "Acatalasemia". Genetics Home Reference. Retrieved 2015-09-28. 6. ^ "OMIM Entry - # 614097 - ACATALASEMIA". www.omim.org. 7. ^ Takahara, S.; Miyamoto, H. Three cases of progressive oral gangrene due to lack of catalase in the blood. Nippon Jibi-Inkoka Gakkai Kaiho 51: 163 only, 1948. ## External links[edit] Classification D * ICD-10: E80.3 * ICD-9-CM: 277.89 * OMIM: 115500 * MeSH: D020642 * DiseasesDB: 30598 * v * t * e Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders Peroxisome biogenesis disorder * Zellweger syndrome * Neonatal adrenoleukodystrophy * Infantile Refsum disease * Adult Refsum disease-2 * RCP 1 Enzyme-related * Acatalasia * RCP 2&3 * Mevalonate kinase deficiency * D-bifunctional protein deficiency * Adult Refsum disease-1 Transporter-related * X-linked adrenoleukodystrophy Lysosomal * Danon disease See also: proteins, intermediates *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Acatalasia

c0268419

wikipedia

https://en.wikipedia.org/wiki/Acatalasia

{"gard": ["363"], "mesh": ["D020642"], "umls": ["C0268419"], "icd-9": ["277.89"], "icd-10": ["E80.3"], "orphanet": ["926"], "wikidata": ["Q3273331"]}

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Hyperkeratinization" – news · newspapers · books · scholar · JSTOR (December 2009) (Learn how and when to remove this template message) Hyperkeratinization (American English or hyperkeratinisation in British) is a disorder of the cells lining the inside of a hair follicle. It is the normal function of these cells to detach or slough off (desquamate) from the skin lining at normal intervals. The dead cells are then forced out of the follicle (primarily by the growing hair). However, in hyperkeratinization, this process is interrupted and a number of these dead skin cells do not leave the follicle because of an excess of keratin, a natural protein found in the skin. This excess of keratin, which is influenced by genetics, results in an increased adherence/bonding of dead skin cells together. This cohesion of cells will block or "cap" the hair follicle (leading to keratosis pilaris) or clog the sebaceous/oil duct (leading to acne). Pathogens may also play a role in causing, perpetuating, or simply taking advantage of this phenomenon, such as virulent sub-strains of Cutibacterium acnes and irregular migration of Staphylococcus epidermidis from the outer surface of the skin into the follicle, where commensal strains of C. acnes exclusively habitate. It itches mildly at times, and strongly at others. Very often it cannot be felt at all.[1][2] ## See also[edit] * hyperkeratosis ## References[edit] 1. ^ Lomholt, H. B.; Kilian, M (2010). "Population genetic analysis of Propionibacterium acnes identifies a subpopulation and epidemic clones associated with acne". PLoS ONE. 5 (8): e12277. doi:10.1371/journal.pone.0012277. PMC 2924382. PMID 20808860. 2. ^ Bek-Thomsen, M; Lomholt, H. B.; Kilian, M (2008). "Acne is not associated with yet-uncultured bacteria". Journal of Clinical Microbiology. 46 (10): 3355–60. doi:10.1128/JCM.00799-08. PMC 2566126. PMID 18716234. This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Hyperkeratinization

None

wikipedia

https://en.wikipedia.org/wiki/Hyperkeratinization

{"wikidata": ["Q5958197"]}

A number sign (#) is used with this entry because Andersen-Tawil syndrome is caused by heterozygous mutation in the KCNJ2 gene (600681) on chromosome 17q24. Description Andersen-Tawil syndrome is an autosomal dominant multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, and distinctive dysmorphic facial or skeletal features. Hypoplastic kidney and valvular heart disease have also been reported. The disorder shows marked intrafamilial variability and incomplete penetrance (summary by Davies et al., 2005). Clinical Features Tawil et al. (1994) used the designation Andersen syndrome for a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. (This Andersen syndrome is not to be confused with Andersen disease, type IV glycogen storage disease (232500).) They found reports of 10 patients and added 4 new patients in 3 kindreds. All the patients had potassium-sensitive periodic paralysis without myotonia indistinguishable from other forms of hyperkalemic periodic paralysis (see 170500). In 1 family, a 45-year-old mother and her 22-year-old son were affected. The son had short stature, low-set ears, hypoplastic mandible, clinodactyly, and scoliosis. The mother was said to have the same dysmorphic features. Tawil et al. (1994) emphasized the variability of both the dysmorphic features and the cardiac manifestations. A variable prolongation of the QT interval, ventricular bigeminy, and short runs of bidirectional ventricular tachycardia were observed. Sudden death in this syndrome was reported by Levitt et al. (1972). Andersen et al. (1971) reported the case of an 8-year-old boy who was short of stature and had hypertelorism, broad nasal root, mandibular hypoplasia, scaphocephaly, and clinodactyly V, as well as a defect of the soft and hard palate. Stubbs (1976) described a 31-year-old housewife with bidirectional ventricular tachycardia whose mother died of 'heart failure' at age 37. Kramer et al. (1979) described a 19-year-old man who had episodes of cardiac dysfunction associated with tetraparesis. A brother had died at age 16 from a heart condition and an older surviving brother suffered from a 'heart condition' similar to that in the proband. The father had experienced attacks of weakness that decreased in frequency with advancing age. Tawil et al. (1994) showed that the Andersen syndrome is distinct from other forms of potassium-sensitive periodic paralysis by demonstrating lack of genetic linkage and concluded that it is probably distinct from the long QT syndrome (192500) on the same basis. Sansone et al. (1997) reported 11 patients from 5 kindreds with the classic triad of potassium-sensitive periodic paralysis, ventricular arrhythmia, and an unusual facial appearance. In these patients, periodic paralysis was associated with low, normal, or high serum potassium levels. A long QTc was observed in almost every case, suggesting this as a minimal diagnostic sign. Canun et al. (1999) suggested that recognition of the characteristic face in Andersen syndrome permits an early diagnosis and the detection of the severe systemic manifestations associated with the syndrome. They described a family in which 10 persons in 3 generations had Andersen syndrome. Facial photographs of 10 affected members of the family were presented. Severity of the facial involvement was not correlated with the severity of heart or muscle involvement of the affected members. Age of onset of periodic paralysis ranged from 4 to 18 years. All affected members with periodic paralysis were responsive to oral potassium except 1, who had normal potassium levels during an attack of paralysis. Two members of the family had no periodic paralysis but had hyperthyroidism. Canun et al. (1999) found a long QTc in only 3 of 8 affected members studied. Canun et al. (1999) did not find short stature; low weight and a slender constitution were found in several relatives. Tristani-Firouzi et al. (2002) presented extensive clinical and in vitro electrophysiologic studies on a total of 17 kindreds with 10 different mutations. Among mutation carriers, the frequency of periodic paralysis was 64% (23 of 36 individuals). Unlike hypokalemic periodic paralysis (170400), in which attacks are precipitated by carbohydrate ingestion, no consistent trigger could be identified in Andersen syndrome. Rest following physical exertion was a common trigger, as in the classic forms of periodic paralysis. At least 2 dysmorphic features were present in 28 of 36 KCNJ2 mutation carriers (78%): 14 of 36 (39%) had low-set ears, 13 of 36 (36%) had hypertelorism, 16 of 36 (44%) had small mandibles, 23 of 36 (64%) had clinodactyly, and 4 of 36 (11%) had syndactyly. Cleft palate was identified in 3 of 36 Andersen syndrome subjects (8%) and scoliosis in 4 of 36 (11%). Dysmorphic features were most often mild and nondisfiguring, and were easily overlooked on routine physical examination. This is relevant given that in individuals with cardiac involvement, one-sixth demonstrated mild dysmorphic features as the only other clue to the diagnosis of Andersen syndrome. In this series, LQT was present in 71% of KCNJ2 mutation carriers, with ventricular arrhythmias present in 64%. Andelfinger et al. (2002) identified a heterozygous missense mutation (R67W; 600681.0006) in the KCNJ2 gene in 41 members of a kindred with ventricular arrhythmias (13 of 16 female members, 81%) and periodic paralysis (10 of 25 male members, 40%) segregating as autosomal dominant traits with sex-specific variable expressivity. Some mutation carriers exhibited dysmorphic features, including hypertelorism, small mandible, syndactyly, clinodactyly, cleft palate, and scoliosis, which, together with cardiodysrhythmic periodic paralysis, constitute Andersen syndrome. However, no individual exhibited all manifestations of Andersen syndrome, and this diagnosis was not considered in the proband until other family members were examined. Other features seen in this kindred included unilateral dysplastic kidney and cardiovascular malformation (i.e., bicuspid aortic valve, bicuspid aortic valve with coarctation of the aorta, or valvular pulmonary stenosis), which had not previously been associated with Andersen syndrome. Nonspecific electrocardiographic abnormalities were identified in some individuals, but none had a prolonged QT interval. Davies et al. (2005) reported 22 affected individuals from 11 unrelated families with ATS. Most patients showed the common clinical triad of hypokalemic periodic paralysis, ventricular arrhythmias, and dysmorphic features, such as hypertelorism, broad-based nose, hypoplastic mandible, and clinodactyly. Other unusual clinical features included poor dentition with abnormal enamel formation in 2 families, high-pitched voice in 1 family, learning disabilities in 1 family, gait ataxia in 1 patient, and renal tubular defects in 1 patient, Genetic analysis identified 9 different pathogenic mutations in the KCNJ2 gene, including 6 novel mutations. In vitro functional expression studies of 5 of the mutant proteins showed a dominant-negative effect on the wildtype allele. In a father and 2 daughters with Andersen syndrome, Lu et al. (2006) identified heterozygosity for a missense mutation in the KCNJ2 gene (T75R; 600681.0011). The mutation was not found in the girls' unaffected mother and brother. In vitro studies revealed that the mutant channel was nonfunctional, and T75R transgenic mice had bidirectional ventricular tachycardia after induction and longer QT intervals. All 3 affected individuals had ventricular arrhythmias and dysmorphic features, but only 2 had periodic paralysis. None of the family members had a prolonged QTc interval, but prominent U waves could be observed in the 3 affected members. Yoon et al. (2006) prospectively evaluated 10 individuals with confirmed mutations in the KCNJ2 gene and identified a characteristic pattern of craniofacial features and dental and skeletal anomalies. These included broad forehead, short palpebral fissures, relatively long nose with fullness along the bridge and bulbous tip, malar, maxillary, and mandibular hypoplasia, thin upper lip, high-arched or cleft palate, triangular facies, and mild facial asymmetry. Dental anomalies were identified in all patients and consisted of delayed eruption of permanent dentition, oligodontia, and dental root anomalies. Jaw characteristics included small maxilla and mandible, narrow upper and lower dental arches, and antegonial notching of the lower border of the mandible. Skeletal anomalies included hand and foot size at the lower limits of normal, brachydactyly, 2-3 toe syndactyly, and toe clinodactyly. Yoon et al. (2006) proposed that the diagnostic dysmorphology criteria of ATS be extended to include these features. Bendahhou et al. (2007) reported 2 unrelated families with periodic paralysis and cardiac dysrhythmias without significant dysmorphic features. The 19-year-old male proband in 1 family had a small chin but no other noticeable dysmorphism. His first episode of periodic paralysis was triggered by corticosteroid treatment of a skin condition, with improvement after discontinuation of corticosteriods; since that time, he had several more attacks, including another one triggered by corticosteroids. Electromyography showed a typical hypokalemic periodic paralysis pattern. The other proband was a 23-year-old woman with no noticeable dysmorphic features who had difficulty playing sports in childhood, with pain in the lower extremities that made it difficult to walk for a few days afterward. On examination, she had full strength of upper limbs but a permanent motor deficit of the lower limbs. Electrocardiography showed ventricular arrhythmia, bidirectional tachycardia, and extrasystoles. Her mother, maternal aunt, and maternal grandmother all had a history of cardiac arrhythmias, and the grandmother had a pacemaker. Other Features In a prospective evaluation of neurocognition in 10 individuals with Andersen-Tawil syndrome aged 8 to 45 years, Yoon et al. (2006) found evidence for neurocognitive deficits compared to unaffected sibs. There was no difference between the 2 groups on tests of verbal or visual memory, and no patients had an abnormal EEG. Although patients and sibs had similar IQ scores in the normal range, patients reported more school difficulties. Detailed neurocognitive testing showed that patients with ATS had decreased scores on tests of executive functioning, matrix reasoning, mathematics, and reading. Six of the 7 adult patients completed high school, 4 of whom completed 1 or more years of post-secondary or technical education. Five of the 7 adults held full-time jobs at the time of the study. Chan et al. (2010) reported a 3-generation Taiwanese family with ATS confirmed by genetic analysis. The 35-year-old female proband had periodic paralysis, characteristic facial features, and long QT syndrome and also had major depression with suicide ideation, hyperreflexia with extensor plantar responses, and evidence of demyelination with periventicular and subcortical white matter lesions on brain MRI. Her 8-year-old affected son had borderline decreased executive function and learning disability. Chan et al. (2010) suggested that neuropsychiatric involvement in ATS may be underestimated, and postulated a role for the KCNJ2 gene in proper myelination and neuronal function. Clinical Management In a young woman with Andersen syndrome and an R218W mutation in the KCNJ2 gene (600681.0002), Junker et al. (2002) observed that amiodarone and acetazolamide treatment resulted in marked and long-lasting improvement of cardiac and muscular symptoms. Mapping Using 400 polymorphic markers across the entire genome in 15 individuals of a kindred with Andersen syndrome, Plaster et al. (2001) mapped the disease locus to chromosome 17q23 (maximum lod of 3.23 at theta = 0.0 for D17S949) near the KCNJ2 gene. Molecular Genetics In a kindred with Andersen syndrome showing linkage to 17q23, Plaster et al. (2001) identified a missense mutation in the KCNJ2 gene (600681.0001). They identified 8 additional mutations in the KCNJ2 gene in unrelated patients with Andersen syndrome (see, e.g., 600681.0002-600681.0005). Using targeted mutation, Lopes et al. (2002) established that mutations in KCNJ2 residues decreased the strength of channel interactions with phosphatidylinositol 4,5-bisphosphate (PIP2). They concluded that a decrease in channel-PIP2 interactions underlies the molecular mechanism of Andersen syndrome when these mutations are present in patients. Among 17 unrelated probands with clinical symptoms of ATS, Donaldson et al. (2003) identified 8 different mutations, including 6 novel mutations, in the KCNJ2 gene in 9 probands. Six probands possessed mutations of residues implicated in binding membrane-associated PIP2. Including previous reports, the authors determined that mutations in PIP2-related residues accounted for disease in 18 of 29 (62%) reported families with KCNJ2-related ATS. Donaldson et al. (2003) found no phenotypic differences between patients with mutations in the PIP2-related residues and those with mutations elsewhere in the gene. The authors suggested that genetic heterogeneity likely exists for this disorder. Choi et al. (2007) identified 2 different heterozygous missense mutations in the KCNJ2 gene in affected members of 2 Korean families with Andersen-Tawil syndrome. The authors stated that this was the first report of causative mutations in KCNJ2 in Korean ATS patients. In 2 unrelated probands with periodic paralysis and cardiac dysrhythmias, who were known to be negative for common CACNA1S and SCN4A mutations causing hypokalemic periodic paralysis, Bendahhou et al. (2007) identified heterozygosity for 2 different missense mutations in the KCNJ2 gene (600681.0012 and 600681.0013, respectively). Bendahhou et al. (2007) noted that except for a small chin in 1 proband, there were no dysmorphic features in these families, and suggested that KCNJ2 should be screened in patients with periodic paralysis even when the classic dysmorphic features of Andersen syndrome are not present. INHERITANCE \- Autosomal dominant GROWTH Height \- Stature (<10th percentile) HEAD & NECK Head \- Small head circumference (lower end of normal) \- Microcephaly Face \- Broad forehead \- Micrognathia \- Malar hypoplasia \- Maxillary hypoplasia \- Triangular face \- Mild facial asymmetry Ears \- Low-set ears \- Preauricular pits Eyes \- Hypertelorism \- Short palpebral fissures Nose \- Bulbous nasal tip Mouth \- Thin upper lip \- Cleft palate \- High-arched palate Teeth \- Persistent primary teeth \- Delayed eruption of secondary teeth \- Oligodontia \- Elongated roots with open apices \- Enamel hypoplasia \- Anterior crossbite CARDIOVASCULAR Heart \- Palpitations \- Prominent U wave \- Prolonged QTc \- Bidirectional ventricular ectopy \- Syncope CHEST Ribs Sternum Clavicles & Scapulae \- Gracile ribs \- Scapular winging SKELETAL \- Joint laxity \- Delayed bone age Skull \- Prominent frontal sinuses \- Short mandibular rami \- Condylar resorption \- Copper beaten skull \- Small maxilla \- Small mandible \- Antegonial notching of mandible Spine \- Scoliosis Limbs \- Gracile long bones Hands \- Small hands \- Fifth finger clinodactyly \- Syndactyly \- Short phalanges \- Short metacarpals \- Brachydactyly Feet \- Small feet \- Syndactyly (2-3) \- Fifth toe clinodactyly \- Short metatarsals NEUROLOGIC Central Nervous System \- Periodic paralysis, usually hypokalemic \- Episodes of weakness can last 1 day to several weeks and can occur 1-3 times per month \- White matter lesions (1 patient) Behavioral Psychiatric Manifestations \- Learning disabilities, mild (some patients) \- Depression (1 patient) LABORATORY ABNORMALITIES \- Hypokalemia during periodic paralysis (most patients) MISCELLANEOUS \- Clinical triad - dysmorphic features, cardiac arrhythmia, and potassium-sensitive periodic paralysis \- Onset of periodic paralysis (mean) 5 years (range) 8 months to 15 years \- Periodic paralysis triggered by exercise, rest following exercise, prolonged periods of rest, and stress MOLECULAR BASIS \- Caused by mutation in the potassium channel, inwardly rectifying, subfamily J, member 2 gene (KCNJ2, 600681.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

ANDERSEN CARDIODYSRHYTHMIC PERIODIC PARALYSIS

c1563715

omim

https://www.omim.org/entry/170390

{"doid": ["0050434"], "mesh": ["D050030"], "omim": ["170390"], "orphanet": ["37553"], "synonyms": ["Alternative titles", "ANDERSEN SYNDROME", "LONG QT SYNDROME 7", "ANDERSEN-TAWIL SYNDROME", "PERIODIC PARALYSIS, POTASSIUM-SENSITIVE CARDIODYSRHYTHMIC TYPE"], "genereviews": ["NBK1264", "NBK1129"]}

Metabolic medical condition Lactic acidosis L-(+)-lactic acid SpecialtyEndocrinology Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's oxidative metabolism. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, Kussmaul breathing (laboured and deep), and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death. ## Contents * 1 Classification * 2 Signs and symptoms * 3 Causes * 4 Pathophysiology * 5 Diagnosis * 6 Treatment * 7 Prognosis * 8 Other animals * 8.1 Reptiles * 8.2 Ruminants * 9 References * 10 External links ## Classification[edit] The Cohen–Woods classification categorizes causes of lactic acidosis as:[1] * Type A: Decreased tissue oxygenation (e.g., from decreased blood flow) * Type B * B1: Underlying diseases (sometimes causing type A) * B2: Medication or intoxication * B3: Inborn error of metabolism ## Signs and symptoms[edit] Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids.[2] Symptoms in humans include all those of typical metabolic acidosis (nausea, vomiting, generalized muscle weakness, and laboured and deep breathing).[3] ## Causes[edit] The several different causes of lactic acidosis include:[citation needed] * Genetic conditions * Biotinidase deficiency, multiple carboxylase deficiency, or nongenetic deficiencies of biotin * Diabetes mellitus and deafness * Fructose 1,6-bisphosphatase deficiency * Glucose-6-phosphatase deficiency * GRACILE syndrome * Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes * Pyruvate dehydrogenase deficiency * Pyruvate carboxylase deficiency * Leigh syndrome * Drugs * Linezolid[4] * Paracetamol/acetaminophen poisoning[5] * Metformin: this risk is low (less than 10 cases for 100,000 patient years), but the risk of metformin-induced lactic acidosis (MALA) increases in certain situations where both the plasma levels of metformin are increased and lactate clearance is impaired.[6] The older related and now withdrawn drug phenformin carried a much higher risk of lactic acidosis.[7] * Isoniazid toxicity * Propofol * Epinephrine * Propylene glycol (D-lactic acidosis) * Nucleoside reverse-transcriptase inhibitors * Abacavir/dolutegravir/lamivudine[8] * Emtricitabine/tenofovir[9] * Potassium cyanide (cyanide poisoning) * Fialuridine[10] * Other * Thiamine deficiency (especially during TPN) * Impaired delivery of oxygen to cells in the tissues (e.g., from impaired blood flow (hypoperfusion)) * Bleeding * Polymyositis * Ethanol toxicity * Sepsis * Shock * Advanced liver disease * Diabetic ketoacidosis * Excessive exercise (overtraining) * Regional hypoperfusion (e.g., bowel ischemia or marked cellulitis) * Cancers such as Non-Hodgkin's and Burkitt lymphomas * Pheochromocytoma[2] * Tumor lysis syndrome[11] * D-lactic acidosis due to intestinal bacterial flora production in short gut syndrome ## Pathophysiology[edit] Glucose metabolism begins with glycolysis, in which the molecule is broken down into pyruvate in ten enzymatic steps. A significant proportion of pyruvate is converted into lactate (usually 10:1). The human metabolism produces about 20 mmol/kg of lactate acid every 24 hours. This happens predominantly in tissues (especially muscle) that have high levels of the "A" isoform of the enzyme lactate dehydrogenase (LDHA), which predominantly converts pyruvate into lactate. The lactate is carried by the bloodstream to other tissues where it is converted at the expense of ATP back to pyruvate by the "B" isoform of LDH (LDHB). Firstly there is gluconeogenesis in the liver (as well as the kidney and some other tissues), where pyruvate is converted into glucose; this is known as the Cori cycle. In addition, lactate moved to other tissues enters the citric acid cycle and eventually oxidative phosphorylation, a process that yields ATP.[2] Elevations in lactate are either a consequence of increased production or of decreased metabolism. With regards to metabolism, this predominantly takes place in the liver (70%), which explains that lactate levels may be elevated in the setting of liver disease.[2] In "type A" lactic acidosis, the production of lactate is attributable to insufficient oxygen for aerobic metabolism. If there is no oxygen available for the parts of the glucose metabolism that require oxygen (citric acid cycle and oxidative phosphorylation), excess pyruvate will be converted in excess lactate. In "type B" lactic acidosis the lactate accumulates because there is a mismatch between glycolysis activity and the remainder of glucose metabolism. Examples are situations where the sympathetic nervous system is highly active (e.g. severe asthma).[2] There is controversy as to whether elevated lactate in acute illness can be attributed to tissue hypoxia; there is limited empirical support for this theoretical notion.[12] ## Diagnosis[edit] Acid-base disturbances such as lactic acidosis are typically first assessed using arterial blood gas tests. Testing of venous blood is also available as an alternative as they are effectively interchangeable.[2] Normally resulting lactate concentrations are in the range indicated below:[13] mg/dL mM Venous blood 4.5–19.8 0.5–2.2 Arterial blood 4.5–14.4 0.5–1.6 Lactic acidosis is classically defined as an elevated lactate together with pH < 7.35 and bicarbonate below 20 mmol/l, but this is not required as lactic acidosis may exist together with other acid-base abnormalities that may affect these two parameters.[2] ## Treatment[edit] If elevated lactate is present in acute illness, supporting the oxygen supply and blood flow are key initial steps.[2] Some vasopressors (drugs that augment the blood pressure) are less effective when lactate levels are high, and some agents that stimulate the beta-2 adrenergic receptor can elevate the lactate further.[2] Direct removal of lactate from the body (e.g. with hemofiltration or dialysis) is difficult, with limited evidence for benefit; it may not be possible to keep up with the lactate production.[2] Limited evidence supports the use of sodium bicarbonate solutions to improve the pH (which is associated with increased carbon dioxide generation and may reduce the calcium levels).[2][14] Lactic acidosis caused by inherited mitochondrial disorders (type B3) may be treated with a ketogenic diet and possibly with dichloroacetate (DCA),[15] although this may be complicated by peripheral neuropathy and has a weak evidence base.[16] ## Prognosis[edit] Mild and transient elevations in lactate have limited impact on mortality, whereas sustained and severe lactate elevations are associated with a high mortality.[2] The mortality of lactic acidosis in people taking metformin was previously reported to be 50%, but in more recent reports this was closer to 25%.[17] ## Other animals[edit] ### Reptiles[edit] Reptiles, which rely primarily on anaerobic energy metabolism (glycolysis) for intense movements, can be particularly susceptible to lactic acidosis. In particular, during the capture of large crocodiles, the animals' use of their glycolytic muscles often alter the blood's pH to a point where they are unable to respond to stimuli or move.[18] Cases are recorded in which particularly large crocodiles which put up extreme resistance to capture later died of the resulting pH imbalance.[19] Certain turtle species have been found to be capable of tolerating high levels of lactic acid without suffering the effects of lactic acidosis. Painted turtles hibernate buried in mud or underwater and do not resurface for the entire winter. As a result, they rely on anaerobic respiration to provide the majority of their energy needs.[20] Adaptations in particular in the turtle's blood composition and shell allow it to tolerate high levels of lactic acid accumulation. In the anoxic conditions where anaerobic respiration is dominant, calcium levels in the blood plasma increase.[20] This calcium serves as a buffer, reacting with the excess lactate to form the precipitate calcium lactate. This precipitate is suggested to be reabsorbed by the shell and skeleton, thereby removing it from the bloodstream; studies examining turtles that have been subjected to prolonged anoxic conditions have up to 45% of their lactate stored within their skeletal structure.[20] ### Ruminants[edit] In ruminant livestock, the cause of clinically serious lactic acidosis is different from the causes described above. In domesticated ruminants, lactic acidosis may occur as a consequence of ingesting large amounts of grain, especially when the rumen population is poorly adapted to deal with grain.[21][22][23] Activity of various rumen organisms results in accumulation of various volatile fatty acids (normally, mostly acetic, propionic, and butyric acids), which are partially dissociated.[24] Although some lactate is normally produced in the rumen, it is normally metabolized by such organisms as Megasphaera elsdenii and, to a lesser extent, Selenomonas ruminantium and some other organisms. With high grain consumption, the concentration of dissociated organic acids can become quite high, resulting in rumen pH dropping below 6. Within this lower pH range, Lactobacillus spp. (producing lactate and hydrogen ions) are favored, and M. elsdenii and S. ruminantium are inhibited, tending to result in a considerable rise of lactate and hydrogen ion concentrations in the rumen fluid.[25] The pKa of lactic acid is low, about 3.9, versus, for example, 4.8 for acetic acid; this contributes to the considerable drop in rumen pH which can occur.[24] Because of the high solute concentration of the rumen fluid under such conditions, considerable water is translocated from the blood to the rumen along the osmotic potential gradient, resulting in dehydration which cannot be relieved by drinking, and which can ultimately lead to hypovolemic shock.[21] As more lactate accumulates and rumen pH drops, the ruminal concentration of undissociated lactic acid increases. Undissociated lactic acid can cross the rumen wall to the blood,[26] where it dissociates, lowering blood pH. Both L and D isomers of lactic acid are produced in the rumen;[21] these isomers are metabolized by different metabolic pathways, and activity of the principal enzyme involved in metabolism of the D isomer declines greatly with lower pH, tending to result in an increased ratio of D:L isomers as acidosis progresses.[25] Measures for preventing lactic acidosis in ruminants include avoidance of excessive amounts of grain in the diet, and gradual introduction of grain over a period of several days, to develop a rumen population capable of safely dealing with a relatively high grain intake.[21][22][23] Administration of lasalocid or monensin in feed can reduce risk of lactic acidosis in ruminants,[27] inhibiting most of the lactate-producing bacterial species without inhibiting the major lactate fermenters.[28] Also, using a higher feeding frequency to provide the daily grain ration can allow higher grain intake without reducing the pH of the rumen fluid.[29] Treatment of lactic acidosis in ruminants may involve intravenous administration of dilute sodium bicarbonate, oral administration of magnesium hydroxide, and/or repeated removal of rumen fluids and replacement with water (followed by reinoculation with rumen organisms, if necessary).[21][22][23] ## References[edit] 1. ^ Woods, Hubert Frank; Cohen, Robert (1976). Clinical and biochemical aspects of lactic acidosis. Oxford: Blackwell Scientific. ISBN 0-632-09460-5.[page needed] 2. ^ a b c d e f g h i j k l Kraut, Jeffrey A.; Madias, Nicolaos E. (11 December 2014). "Lactic Acidosis". New England Journal of Medicine. 371 (24): 2309–2319. doi:10.1056/NEJMra1309483. PMID 25494270. 3. ^ MedlinePlus Encyclopedia: Lactic acidosis 4. ^ Santini, A; Ronchi, D; Garbellini, M; Piga, D; Protti, A (July 2017). "Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes". Expert Opinion on Drug Safety. 16 (7): 833–843. doi:10.1080/14740338.2017.1335305. PMID 28538105. 5. ^ Shah, AD; Wood, DM; Dargan, PI (January 2011). "Understanding lactic acidosis in paracetamol (acetaminophen) poisoning". British Journal of Clinical Pharmacology. 71 (1): 20–8. doi:10.1111/j.1365-2125.2010.03765.x. PMC 3018022. PMID 21143497. 6. ^ DeFronzo, R; Fleming, GA; Chen, K; Bicsak, TA (February 2016). "Metformin-associated lactic acidosis: Current perspectives on causes and risk". Metabolism: Clinical and Experimental. 65 (2): 20–9. doi:10.1016/j.metabol.2015.10.014. PMID 26773926. 7. ^ Fimognari, F. L.; Pastorelli, R.; Incalzi, R. A. (2006). "Phenformin-Induced Lactic Acidosis in an Older Diabetic Patient: A recurrent drama (phenformin and lactic acidosis)". Diabetes Care. 29 (4): 950–1. doi:10.2337/diacare.29.04.06.dc06-0012. PMID 16567854. 8. ^ "Triumeq (Abacavir, Dolutegravir, and Lamivudine Film-coated Tablets) Drug Information: Description, User Reviews, Drug Side Effects, Interactions – Prescribing Information at RxList". RxList. Retrieved 2016-03-25. 9. ^ "Truvada". 10. ^ McKenzie, Robin; Fried, Michael W.; Sallie, Richard; Conjeevaram, Hari; Di Bisceglie, Adrian M.; Park, Yoon; Savarese, Barbara; Kleiner, David; Tsokos, Maria; Luciano, Carlos; Pruett, Timothy; Stotka, Jennifer L.; Straus, Stephen E.; Hoofnagle, Jay H. (1995). "Hepatic Failure and Lactic Acidosis Due to Fialuridine (FIAU), an Investigational Nucleoside Analogue for Chronic Hepatitis B". New England Journal of Medicine. 333 (17): 1099–105. doi:10.1056/NEJM199510263331702. PMID 7565947. 11. ^ Darmon, Michael; Malak, Sandra; Guichard, Isabelle; Schlemmer, Benoit (July–September 2008). "Acute tumor lysis syndrome: a comprehensive review". Revista Brasileira de Terapia Intensiva. 20 (3): 278–285. doi:10.1590/S0103-507X2008000300011. ISSN 0103-507X. 12. ^ Garcia-Alvarez, Mercedes; Marik, Paul; Bellomo, Rinaldo (April 2014). "Stress hyperlactataemia: present understanding and controversy". The Lancet Diabetes & Endocrinology. 2 (4): 339–347. doi:10.1016/S2213-8587(13)70154-2. PMID 24703052. 13. ^ Goldman, Lee; Schafer, Andrew (May 11, 2015). Goldman-Cecil Medicine (25 ed.). Elsevier. ISBN 978-1455750177. 14. ^ Boyd, JH; Walley, KR (Aug 2008). "Is there a role for sodium bicarbonate in treating lactic acidosis from shock?". Current Opinion in Critical Care. 14 (4): 379–83. doi:10.1097/MCC.0b013e3283069d5c. PMID 18614899. 15. ^ Stacpoole, PW; Kurtz, TL; Han, Z; Langaee, T (2008). "Role of dichloroacetate in the treatment of genetic mitochondrial diseases". Advanced Drug Delivery Reviews. 60 (13–14): 1478–87. doi:10.1016/j.addr.2008.02.014. PMC 3746325. PMID 18647626. 16. ^ Pfeffer, G; Majamaa, K; Turnbull, DM; Thorburn, D; Chinnery, PF (2012). Chinnery, Patrick F (ed.). "Treatment for mitochondrial disorders". The Cochrane Database of Systematic Reviews. 4 (4): CD004426. doi:10.1002/14651858.CD004426.pub3. PMC 7201312. PMID 22513923. 17. ^ Kajbaf, F; Lalau, JD (November 2014). "Mortality rate in so-called "metformin-associated lactic acidosis": a review of the data since the 1960s". Pharmacoepidemiology and Drug Safety. 23 (11): 1123–7. doi:10.1002/pds.3689. PMID 25079826. 18. ^ Seymour R. S.; Webb G. J. W.; Bennett A. F.; Bradford D. F. (1987). "Chapter 26. Effect of capture on the physiology of Crocodylus porosus" (PDF). In Webb, G. J. W.; Manolis, S. C.; Whitehead, P. J. (eds.). Wildlife Management: Crocodiles and Alligators. Sydney: Surrey Beatty. pp. 253–257. 19. ^ [1]. Accessed 31 January 2009. 20. ^ a b c Jackson, Donald C. (2002). "Hibernating without oxygen: physiological adaptations of the painted turtle". The Journal of Physiology. 543 (3): 731–737. doi:10.1113/jphysiol.2002.024729. PMC 2290531. PMID 12231634. 21. ^ a b c d e Kimberling, C. V. 1988. Jensen and Swift's diseases of sheep. 3rd Ed. Lea & Fibiger, Philadelphia. 394 pp. 22. ^ a b c Pugh, D. G. 2002. Sheep and goat medicine. Saunders. 468 pp. 23. ^ a b c Kahn, C. M. (ed.) 2005. Merck veterinary manual. 9th Ed. Merck & Co., Inc., Whitehouse Station. 24. ^ a b Van Soest, P. J. 1994. Nutritional ecology of the ruminant. 2nd Ed. Cornell Univ. Press, Ithaca. 476 pp. 25. ^ a b Nocek J. E. (1997). "Bovine acidosis: implications on laminitis". J. Dairy Sci. 80: 1005–1028. 26. ^ Owens, FN; Secrist, DS; Hill, WJ; Gill, DR (1998). "Acidosis in cattle: a review". Journal of Animal Science. 76 (1): 275–86. doi:10.2527/1998.761275x. PMID 9464909. 27. ^ Nagaraja, TG; Avery, TB; Bartley, EE; Galitzer, SJ; Dayton, AD (1981). "Prevention of lactic acidosis in cattle by lasalocid or monensin". Journal of Animal Science. 53 (1): 206–16. doi:10.2527/jas1981.531206x. PMID 7319937. 28. ^ Dennis, SM; Nagaraja, TG; Bartley, EE (1981). "Effects of lasalocid or monensin on lactate-producing or -using rumen bacteria". Journal of Animal Science. 52 (2): 418–26. doi:10.2527/jas1981.522418x. PMID 7275867. 29. ^ Kaufmann W (1976). "Influence of the composition of the ration and the feeding frequency on ph-regulation in the rumen and on feed in-take in ruminants". Livestock Prod. Sci. 3: 103–114. ## External links[edit] Classification D * ICD-10: E87.2 * ICD-9-CM: 276.2 * MeSH: D000140 * DiseasesDB: 29145 External resources * MedlinePlus: 000391 * eMedicine: article/768159 * v * t * e Acid–base disorders Acidosis Metabolic * High anion gap * Ketoacidosis * Diabetic ketoacidosis * Alcoholic ketoacidosis * Lactic * Normal anion gap * Hyperchloremic * Renal tubular Respiratory * Respiratory Alkalosis * Metabolic * Contraction alkalosis * Respiratory Other * Mixed disorder of acid-base balance * Acid–base homeostasis *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Lactic acidosis

c0001125

wikipedia

https://en.wikipedia.org/wiki/Lactic_acidosis

{"mesh": ["D000140"], "umls": ["C0001125"], "icd-9": ["276.2"], "wikidata": ["Q1500373"]}

This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (November 2017) Portopulmonary hypertension Other namesPulmonary arterial hypertension associated with portal hypertension SpecialtyPulmonology Portopulmonary hypertension (PPH)[1] is defined by the coexistence of portal and pulmonary hypertension. PPH is a serious complication of liver disease, present in 0.25 to 4% of all patients suffering from cirrhosis. Once an absolute contraindication to liver transplantation, it is no longer, thanks to rapid advances in the treatment of this condition.[2] Today, PPH is comorbid in 4-6% of those referred for a liver transplant.[3][4] ## Contents * 1 Presentation * 2 Pathophysiology * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 References * 7 External links ## Presentation[edit] PPH presents roughly equally in male and female cirrhotics; 71% female in an American series and 57% male in a larger French series.[5][6] Typically, patients present in their fifth decade, aged 49 +/- 11 years on average.[5][7] In general, PPH is diagnosed 4–7 years after the patient is diagnosed with portal hypertension[8] and in roughly 65% of cases, the diagnosis is actually made at the time of invasive hemodynamic monitoring following anesthesia induction prior to liver transplantation.[9] Once patients are symptomatic, they present with right heart dysfunction secondary to pulmonary hypertension and its consequent dyspnea, fatigue, chest pain and syncope.[10] Patients tend to have a poor cardiac status, with 60% having stage III-IV NYHA heart failure.[5] PPH is actually independent of the severity of cirrhosis but may be more common in specific types of cirrhosis, in one series more so in Autoimmune Hepatitis and less in Hepatitis C cirrhosis,[6] while in another it was equally distributed throughout the diagnoses.[4] ## Pathophysiology[edit] PPH pathology arises both from the humoral consequences of cirrhosis and the mechanical obstruction of the portal vein.[11] A central paradigm holds responsible an excess local pulmonary production of vasoconstrictors that occurs while vasodilatation predominates systemically.[12] Key here are imbalances between vasodilatory and vasoconstricting molecules; endogenous prostacyclin and thromboxane (from Kupffer Cells) [13][14] or nitrous oxide (NO) and endothelin-1 (ET-1).[7] ET-1 is the most potent vasoconstrictor under investigation[15] and it has been found to be increased in both cirrhosis[16] and pulmonary hypertension.[17] Endothelin-1 has two receptors in the pulmonary arterial tree, ET-A which mediates vasoconstriction and ET-B which mediates vasodilation. Rat models have shown decreased ET-B receptor expression in pulmonary arteries of cirrhotic and portal hypertensive animals, leading to a predominant vasoconstricting response to endothelin-1.[18] In portal hypertension, blood will shunt from portal to systemic circulation, bypassing the liver. This leaves unmetabolized potentially toxic or vasoconstricting substances to reach and attack the pulmonary circulation. Serotonin, normally metabolized by the liver, is returned to the lung instead where it mediates a smooth muscle hyperplasia and hypertrophy.[19] Moreover, a key pathogenic factor in the decline in status of PPH patients related to this shunting is the cirrhotic cardiomyopathy with myocardial thickening and diastolic dysfunction.[citation needed] Finally, the pulmonary pathology of PPH is very similar to that of primary pulmonary hypertension.[20] The muscular pulmonary arteries become fibrotic and hypertrophy while the smaller arteries lose smooth muscle cells and their elastic intima. One study found at autopsy significant thickening of pulmonary arteries in cirrhotic patients.[21] This thickening and remodeling forms a positive feedback loop that serves to increase PAP and induce right heart hypertrophy and dysfunction. ## Diagnosis[edit] The diagnosis of portopulmonary hypertension is based on hemodynamic criteria: 1. . Portal hypertension and/or liver disease (clinical diagnosis—ascites/varices/splenomegaly) 2. . Mean pulmonary artery pressure—MPAP > 25 mmHg at rest 3. . Pulmonary vascular resistance—PVR > 240 dynes s cm−5 4. . Pulmonary artery occlusion pressure— PAOP < 15mmHg or transpulmonary gradient—TPG > 12 mmHg where TPG = MPAP − PAOP.[22] The diagnosis is usually first suggested by a transthoracic echocardiogram, part of the standard pre-transplantation work-up. Echocardiogram estimated pulmonary artery systolic pressures of 40 to 50 mm Hg are used as a screening cutoff for PPH diagnosis,[23] with a sensitivity of 100% and a specificity as high as 96%.[24] The negative predictive value of this method is 100% but the positive predictive value is 60%.[25] Thereafter, these patients are referred for pulmonary artery catheterization. The limitations of echocardiography are related to the derivative nature of non-invasive PAP estimation. The measurement of PAP by echocardiogram is made using a simplified Bernoulli equation. High cardiac index and pulmonary capillary wedge pressures, however, may lead to false positives by this standard. By one institution’s evaluation, the correlation between estimated systolic PAP and directly measured PAP was poor, 0.49.[26] For these reasons, right heart catheterization is needed to confirm the diagnosis.[citation needed] ## Treatment[edit] In general, the treatment of PPH is derived from the treatment of pulmonary hypertension. The best treatment available is the combination of medical therapy and liver transplantation.[citation needed] The ideal treatment for PPH management is that which can achieve pulmonary vasodilatation and smooth muscle relaxation without exacerbating systemic hypotension. Most of the therapies for PPH have been adapted from the primary pulmonary hypertension literature. Calcium channel blockers, b-blockers and nitrates have all been used – but the most potent and widely used aids are prostaglandin (and prostacyclin) analogs, phosphodiesterase inhibitors, nitric oxide and, most recently, endothelin receptor antagonists and agents capable of reversing the remodeling of pulmonary vasculature.[citation needed] Inhaled nitric oxide vasodilates, decreasing pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) without affecting systemic artery pressure because it is rapidly inactivated by hemoglobin,[27] and improves oxygenation by redistributing pulmonary blood flow to ventilated areas of lung.[28] Inhaled nitric oxide has been used successfully to bridge patients through liver transplantation and the immediate perioperative period, but there are two significant drawbacks: it requires intubation and cannot be used for long periods of time due to methemoglobinemia.[citation needed] Prostaglandin PGE1 (Alprostadil) binds G-protein linked cell surface receptors that activate adenylate cyclase to relax vascular smooth muscle.[29] Prostacyclin – PGI2, an arachadonic acid derived lipid mediator (Epoprostenol, Flolan, Treprostenil) – is a vasodilator and, at the same time, the most potent inhibitor of platelet aggregation.[30] More importantly, PGI2 (and not nitrous oxide) is also associated with an improvement in splanchnic perfusion and oxygenation.[31] Epoprostenol and ilioprost (a more stable, longer acting variation[32]) can and does successfully bridge for patients to transplant.[33] Epoprostenol therapy can lower PAP by 29-46% and PVR by 21-71%.,[34] Ilioprost shows no evidence of generating tolerance, increases cardiac output and improves gas exchange while lowering PAP and PVR.[35] A subset of patients does not respond to any therapy, likely having fixed vascular anatomic changes.[citation needed] Phosphodiesterase inhibitors (PDE-i) have been employed with excellent results. It has been shown to reduce mean PAP by as much as 50%,[36] though it prolongs bleeding time by inhibiting collagen-induced platelet aggregation.[37] Another drug, Milrinone, a Type 3 PDE-i increases vascular smooth muscle adenosine-3,5-cyclic monophosphate concentrations to cause selective pulmonary vasodilation.[38] Also, by causing the buildup of cAMP in the myocardium, Milrinone increases contractile force, heart rate and the extent of relaxation. The newest generation in PPH pharmacy shows great promise. Bosentan is a nonspecific endothelin-receptor antagonist capable of neutralizing the most identifiable cirrhosis associated vasoconstrictor,[39] safely and efficaciously improving oxygenation and PVR,[40][41] especially in conjunction with sildenafil.[42] Finally, where the high pressures and pulmonary tree irritations of PPH cause a medial thickening of the vessels (smooth muscle migration and hyperplasia), one can remove the cause –control the pressure, transplant the liver – yet those morphological changes persist, sometimes necessitating lung transplantation. Imatinib, designed to treat chronic myeloid leukemia, has been shown to reverse the pulmonary remodeling associated with PPH.[4][43][44] ## Prognosis[edit] Following diagnosis, mean survival of patients with PPH is 15 months.[45] The survival of those with cirrhosis is sharply curtailed by PPH but can be significantly extended by both medical therapy and liver transplantation, provided the patient remains eligible. Eligibility for transplantation is generally related to mean pulmonary artery pressure (PAP). Given the fear that those PPH patients with high PAP will suffer right heart failure following the stress of post-transplant reperfusion or in the immediate perioperative period, patients are typically risk-stratified based on mean PAP. Indeed, the operation-related mortality rate is greater than 50% when pre-operative mean PAP values lie between 35 and 50 mm Hg; if mean PAP exceeds 40-45, transplantation is associated with a perioperative mortality of 70-80% (in those cases without preoperative medical therapy).[46][24] Patients, then, are considered to have a high risk of perioperative death once their mean PAP exceeds 35 mm_Hg.[47] Survival is best inferred from published institutional experiences. At one institution, without treatment, 1-year survival was 46% and 5-year survival was 14%. With medical therapy, 1-year survival was 88% and 5-year survival was 55%. Survival at 5 years with medical therapy followed by liver transplantation was 67%.[22] At another institution, of the 67 patients with PPH from 1652 total cirrhotics evaluated for transplant, half (34) were placed on the waiting list. Of these, 16 (48%) were transplanted at a time when 25% of all patients who underwent full evaluation received new livers, meaning the diagnosis of PPH made a patient twice as likely to be transplanted, once on the waiting list. Of those listed for transplant with PPH, 11 (33%) were eventually removed because of PPH, and 5 (15%) died on the waitlist. Of the 16 transplanted patients with PPH, 11 (69%) survived for more than a year after transplant, at a time when overall one-year survival in that center was 86.4%. The three year post-transplant survival for patients with PPH was 62.5% when it was 81.02% overall at this institution.[4] ## References[edit] 1. ^ Adapted from: Tapper EB: http://wikidoc.org/index.php/Portopulmonary_hypertension 2. ^ Kuo PC et al. Portopulmonary Hypertension and the Liver Transplant Candidate. Transplantation 1999;67(8):1087-1093 3. ^ Torregrosa M et al. Role of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplant candidates. Transplantation 2001;71:572-574 4. ^ a b c d Tapper EB, Knowles D, Heffron T, Lawrence EC, Csete M. Portopulmonary hypertension: imatinib as a novel treatment and the Emory experience with this condition. Transplant Proc. 2009 Jun;41(5):1969-71. 5. ^ a b c Le Pavec et al. Portopulmonary Hypertension: Survival and Prognostic Factors. Am J Respir Crit Care Med Vol 178. pp 637–643, 2008 6. ^ a b Kawut SM et al. Clinical Risk Factors for Portopulmonary Hypertension. Hepatology 2008;48 7. ^ a b Bejaminov et al. Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Gut 2003; 52:1355-1362 8. ^ Hadengue et al. PH complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991;100:520-528 9. ^ Hadengue et al. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology 1991;100:520-528 10. ^ Martinex-Palli et al. Liver Transplant in High Risk Patients. Transplant Proceedings 2005;37:3861-3864 11. ^ Budhiraja et al. Portopulmonary Hypertension: A Tale of Two Circulations. Chest. 2003;123:562-576. 12. ^ Moller et al. Cardiopulmonary complications in chronic liver disease. World J Gastroenterol 2006;12;526-538 13. ^ Christman et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992;327:1774-78 14. ^ Maruyama et al. Thromboxane-dependent portopulmonary hypertension. Am J Med. 2005;118:93-94 15. ^ Giaid A. Nitrous oxide and endothelin-1 in pulmonary hypertension. Chest. 1998;114;208-12S 16. ^ Gerbes. ET1 and 3 plasma conc in patients with cirrhosis: role of splanchnic and renal passage and liver function. Hepatology 1995;21:735-9 17. ^ Stewart. Increase plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med 1991;114:464-9 18. ^ Luo et al. Increased pulmonary vascular ETb receptor expression and responsiveness to ET-1 in cirrhotive and portal hypertensive rats. J Hepatol 2003;38:556-63 19. ^ Egermayer et al. Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension. Thorax 1999;54:161-168 20. ^ Schraufnagel DE, Kay JM. Structural and pathologic changes in lung vasculature in chronic liver disease. Clin Chest Med 1996; 17: 1 21. ^ Matsubara O, Nakamura T, Uehara T, Kasuga T. Histometrical investigations of the pulmonary artery in severe hepatic disease. J Pathol 1984; 143: 31. 22. ^ a b Swanson KL et al. Survival in Portopulmonary Hypertension: Mayo Clinic Experience Categorized by Treatment Subgroups. Am J Transpl 2008; 8: 2445–2453 23. ^ Torregosa et al. Role of Doppler echos in the assessment of PPHTN in liver transplant candidates. Transplantation 2001;71:572-574 24. ^ a b Kim et al. Accuracy of Doppler Echos in the assessment of PTHN in liver transplant candidates. Liver Transplant. 6:453, 2000 25. ^ Colle et al. Diagnosis of portopulmonary hypertension in candidates for liver transplant: a prospective study. Hepatology 2003;37:401-209 26. ^ Tapper EB, unpublished data 27. ^ Steudel et al. Inhaled nitric oxide: Basic biology and clinical applications. Anesthesiology 1999;91:1090-121 28. ^ Lowson. Inhaled alternative to nitric oxide. Anesthesiology 2002;96:1504-13 29. ^ Kerins et al. Prostacyclin and Prostaglandin E1: Molecular mechanisms and therapeutic utility. Prog Hemostasis Thrombosis 1991;10:307-37 30. ^ Vane et al. Pharmacodynamic profile of prostacyclin. Am J Cardiol 1995;75:3A-10A 31. ^ Eichelbronner et al. Aerosolized prostacyclin and INO in septic shock: Different effects on splanchnic oxygenation. Intensive Care Med 1996;22:880-7 32. ^ Minder et al. Intravenous ilioprost bridging to orthotopic liver transplant in portopulmonary hypertension. Eur Respir J 2004;24:703-707 33. ^ et al. Successful use of chronic epoprostenol as a bridge to liver transplant in severe PPHTN. Transplant 1998 4:457 34. ^ Kuo PC, Johnson LB, Plotkin JS, Howell CD, Bartlett ST, Rubin LJ. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation 1997; 63: 604 35. ^ Lowson. Inhaled alternative to nitrous oxide. Anesthesiology 2002;96:1504-13 36. ^ Makisalo et al. Sildenafil for portopulmonary hypertension in a patient undergoing liver Transplant. Liver Transplant. 2004;10:945-950 37. ^ Berkels et al. Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil. J Cardiovasc Pharmacolo 2001;37:413-421 38. ^ Haraldsson et al. The additive pulmonary vasodilatory effect of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Aesth Analg 2001;93:1439-45 39. ^ Rubin et al. Bosentan therapy for Pulmonary arterial hypertension. N Engl J Med 2002;346:896-903 40. ^ Hoeper et al. Bosentan therapy for portopulmonary hypertension. Eur Respir J. 2005;25:502-8 41. ^ Kuntzen. Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: a safe and effective therapy? Gastroenterology. 2005;128:164-8 42. ^ Wilkins et al.Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med. 2005;171:1292-7 43. ^ Schermuly et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J. Clin. Invest. 115:2811-2821 (2005). 44. ^ Ghofrani et al. Imatinib for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2005; 353:1412-1413 45. ^ Ramsay et al. Severed PHTN in liver Transplant candidates. Liver Transplant Surg 1997 3:494 46. ^ Csete M. Intraoperative management of liver transplant patients with pulmonary hypertension. Liver Transplant Surg 1997:3:454-55 47. ^ Krowka et al. Pulm Hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver Transplant. Liver Transpl 2000;6:443-450 ## External links[edit] Classification D * ICD-10: I27.2 External resources * Orphanet: 275813 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Portopulmonary hypertension

c1868851

wikipedia

https://en.wikipedia.org/wiki/Portopulmonary_hypertension

{"umls": ["C1868851"], "orphanet": ["275813"], "wikidata": ["Q7232210"]}

A number sign (#) is used with this entry because of evidence that Rahman syndrome (RMNS) is caused by heterozygous mutation in the HIST1H1E gene (142220) on chromosome 6p22. Description Rahman syndrome is characterized by mild to severe intellectual disability associated with variable somatic overgrowth manifest as increased birth length, height, weight, and/or head circumference. The overgrowth is apparent in infancy and may lessen with time or persist. The phenotype is highly variable; some individuals may have other minor anomalies, including dysmorphic facial features, strabismus, or camptodactyly. The disorder is thought to result from a defect in epigenetic regulation (summary by Tatton-Brown et al., 2017). Clinical Features Tatton-Brown et al. (2017) reported 5 unrelated patients, ranging in age from 1.9 to 16 years, with mild to severe intellectual disability associated with variable somatic overgrowth, including height, weight, and/or head circumference. Two patients showed increased height and/or head circumference early in life, which normalized in the teenage years, whereas the other 3 patients continued to have increased somatic parameters, particularly head circumference (+1.8 to +3.7 SD). Three patients were hypotonic in the neonatal period and 1 was hypertonic. They had similar facial features, including full cheeks, high hairline, and telecanthus. Additional features, each found only in 1 or 2 patients, included kyphoscoliosis, camptodactyly, talipes equinovarus, advanced bone age, dental anomalies, skin nevi, strabismus, astigmatism, and amblyopia. It was unclear if these additional features were related to the mutation or were coincidental. Molecular Genetics In 5 unrelated patients with Rahman syndrome, Tatton-Brown et al. (2017) identified 3 different heterozygous truncating mutations in the HIST1H1E gene (142220.0001-142220.0003). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, occurred de novo in 4 families; parental DNA from the fifth family was not available. The mutations not found in the ExAC database or in an in-house database of 11,677 exomes. All of the mutations resulted in the generation of a similar protein truncated in the C-terminal domain, which is involved in chromatin binding and protein-protein interactions. The truncated proteins were predicted to have a reduced net charge compared to the wildtype protein, rendering them likely to be less effective in neutralizing negatively charged linker DNA. Moreover, truncation of the C terminus would likely impede DNA binding and protein-protein interactions. The patients were ascertained from a cohort of 710 individuals with intellectual disability and height and/or head circumference equal to or greater than +2 SD, or 'unspecified overgrowth,' who underwent genetic studies; HIST1H1E mutations accounted for 0.7%. Functional studies of the variants and studies of patient cells were not performed. INHERITANCE \- Autosomal dominant GROWTH Height \- Increased birth length \- Increased height Weight \- Increased birth weight \- Increased weight HEAD & NECK Head \- Large head circumference Face \- Full cheeks Eyes \- Telecanthus \- Strabismus \- Amblyopia \- Astigmatism ABDOMEN Gastrointestinal \- Poor feeding in the neonatal period SKELETAL \- Advanced bone age Spine \- Kyphoscoliosis Hands \- Camptodactyly Feet \- Talipes equinovarus SKIN, NAILS, & HAIR Skin \- Nevi MUSCLE, SOFT TISSUES \- Hypotonia, neonatal \- Hypertonia, neonatal NEUROLOGIC Central Nervous System \- Delayed development \- Intellectual disability, mild to severe MISCELLANEOUS \- Highly variable features \- De novo mutation MOLECULAR BASIS \- Caused by mutation in the histone gene cluster 1, H1 histone family, member E gene (HIST1H1E, 142220.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

RAHMAN SYNDROME

c4479637

omim

https://www.omim.org/entry/617537

{"omim": ["617537"]}

Childhood disintergrative disorder is a rare pervasive developmental disorder with a disease onset before the age of three and characterized by a dramatic loss of behavioral and developmental functioning after atleast two years of normal development. Manifestations of the disease include loss of speech, incontinence, communication and social interaction problems, stereotypical autistic behaviors and dementia. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Childhood disintegrative disorder

c0236791

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=168782

{"gard": ["6040"], "umls": ["C0236791"], "icd-10": ["F84.3"], "synonyms": ["Dementia infantilis", "Heller syndrome"]}

Childhood granulomatous periorificial dermatitis Other namesGianotti-type perioral dermatitis or Facial Afro-Caribbean childhood eruption SpecialtyDermatology Childhood granulomatous periorificial dermatitis (CGPD), is a rare benign granulomatous skin disease of unknown cause.[1] The disorder was first described in 1970 by Gianotti in a case series of five children.[2] CGPD is more common in boys than girls.[3] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Prognosis * 6 Epidemiology * 7 History * 8 See also * 9 References ## Signs and symptoms[edit] CGPD is characterized by the presence of small, raised, dome-shaped, flesh-colored or yellow-brown papules primarily distributed around the mouth, eyes, and nose.[1] Affected children may also have papules on the ears, eyelids, cheeks, forehead, and nose.[1] CGPD skin lesions rarely affect areas of the skin other than the face.[1] ## Cause[edit] The cause of CGPD is unknown.[3] ## Diagnosis[edit] The approach to diagnosing CGPD is controversial.[2] Certain dermatologists suggest that ruling out infectious and allergic causes of similar skin eruptions and a skin biopsy demonstrating features consistent with CGPD is adequate for diagnosis. In contrast, other dermatologists advocate for performing a complete history and physical examination and obtaining laboratories and appropriate imaging to rule out cutaneous sarcoidosis.[2] On microscopy, non-tuberculous granulomas with surrounding lymphocytes clustered around hair follicles may be seen; additionally, infiltrates of epithelioid macrophages, lymphocytes, and giant cells may also be seen.[2][3] Several conditions exhibit skin findings similar to those of CGPD. These conditions include perioral dermatitis, acne vulgaris, granulomatous rosacea, contact dermatitis, folliculitis, atopic dermatitis, cheilitis, medication-induced acneiform eruptions, lupus miliaris disseminatus faciei, benign cephalic histiocytosis, granulosis rubra nasi, xanthomas, zinc deficiency, glucagonoma, cutaneous sarcoidosis, and scabies.[2][3] ## Treatment[edit] Treatment recommendations for CGPD vary and may include observation without treatment, stopping the use of topical corticosteroids, and the use of topical or oral antibiotics as well as isotretinoin.[2] Topical antibiotics such as metronidazole and erythromycin have been used for CGPD.[2] Oral antibiotics of the tetracycline class such as minocycline, doxycycline, and tetracycline have been recommended for CGPD.[1] Trimethoprim/sulfamethoxazole has also been used.[2] The use of oral systemic antibiotics is limited by side effects such as nausea, vomiting, and sensitivity of the skin to sunlight.[1] Tetracycline antibiotics are not recommended for children under the age of 8 since tetracyclines are known to deposit in teeth (thereby staining them) and impair bone growth in children.[1] The use of calcineurin inhibitor creams such as tacrolimus or pimecrolimus on the skin is controversial and results have been mixed.[1] Certain studies found the use of topical calcineurin inhibitors led to resolution of CGPD whereas others saw incomplete resolution or prolonged symptoms.[1] Topical azelaic acid has been used successfully to treat CGPD.[1] Immediate discontinuation of topical corticosteroids is recommended since corticosteroids are thought to worsen CGPD.[2] ## Prognosis[edit] CGPD is known to be a temporary skin disease with a benign course.[1] The skin papules typically resolve after a few months to a few years. After CGPD resolves, the skin may return to normal without scarring or may have small atrophic depressions with collagen loss, milia, or small pit-like scars.[1] ## Epidemiology[edit] CGPD occurs most often in children of Afro-Caribbean descent before puberty though reports of this disease occurring in Asian and Caucasian children have also been described.[1][3] Due to the limited number of reported cases, it remains controversial whether CGPD occurs more often in African children than in children of other races.[2] CGPD is more common in boys than girls.[3] ## History[edit] Gianotti et al. first described CGPD in five Italian children in 1970.[3] In 1990, Williams et al. described a similar skin eruption in five children of Afro-Caribbean descent and coined the proposed term "facial Afro-Caribbean childhood eruption (FACE)".[3] Subsequently, another article by Katz and Lesher first introduced the term CGPD since some reported cases were not found in children of Afro-Caribbean descent and to avoid confusion with perioral dermatitis.[3] ## See also[edit] * Perioral dermatitis ## References[edit] 1. ^ a b c d e f g h i j k l m Dessinioti, C; Antoniou, C; Katsambas, A (January–February 2014). "Acneiform eruptions". Clinics in Dermatology (Review). 32 (1): 24–34. doi:10.1016/j.clindermatol.2013.05.023. PMID 24314375. 2. ^ a b c d e f g h i j Zalaudek, I; Di Stefani, A; Ferrara, G; Argenziano, G (April 2005). "Childhood granulomatous periorificial dermatitis: a controversial disease". Journal of the German Society of Dermatology (Review). 3 (4): 252–5. doi:10.1111/j.1610-0387.2005.05009.x. PMID 16370472. S2CID 9802651. 3. ^ a b c d e f g h i Kim, YJ; Shin, JW; Lee, JS; Park, YL; Whang, KU; Lee, SY (August 2011). "Childhood granulomatous periorificial dermatitis". Annals of Dermatology (Review). 23 (3): 386–8. doi:10.5021/ad.2011.23.3.386. PMC 3162274. PMID 21909215. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Childhood granulomatous periorificial dermatitis

None

wikipedia

https://en.wikipedia.org/wiki/Childhood_granulomatous_periorificial_dermatitis

{"wikidata": ["Q30314291"]}

NPHP3-related Meckel-like syndrome is a rare, genetic, syndromic renal malformation characterized by cystic renal dysplasia with or without prenatal oligohydramnios, central nervous system abnormalities (commonly Dandy-Walker malformation), congenital hepatic fibrosis, and absence of polydactyly. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

NPHP3-related Meckel-like syndrome

c2673885

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3032

{"gard": ["4665"], "mesh": ["C537756"], "omim": ["267010"], "umls": ["C2673885"], "icd-10": ["Q61.9"], "synonyms": ["Goldston syndrome", "Meckel syndrome type 7", "Meckel-like syndrome type 1", "Renal-hepatic-pancreatic dysplasia-Dandy-Walker cysts syndrome"]}

## Summary ### Clinical characteristics. The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes the following phenotypes: * Metaphyseal dysplasia without hypotrichosis (MDWH) * Cartilage-hair hypoplasia (CHH) * Anauxetic dysplasia (AD) CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis. The most severe phenotype, AD, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family. ### Diagnosis/testing. Diagnosis of the CHH-AD spectrum disorders is based on clinical findings, characteristic radiographic findings, and in some cases, evidence of immune dysfunction, macrocytic anemia, and/or gastrointestinal problems. If clinical and radiographic findings are inconclusive, identification of biallelic pathogenic variants in RMRP by molecular genetic testing can confirm the diagnosis and allow for family studies. ### Management. Treatment of manifestations: * In the newborn. Hypoplastic anemia may require repeated blood transfusions; congenital megacolon or Hirschsprung disease may require surgical resection. * In childhood. Surgery may be needed to fuse unstable cervical vertebrae and/or to treat progressive kyphoscoliosis that compromises lung function in AD; corrective osteotomies may be required to treat progressive varus deformity associated with ligament laxity in the knees. Pubertal maturation may be delayed and may require hormonal induction. * For those with immunodeficiency. Treatment of underlying infections based on their type, location, and severity; immediate antiviral treatment with intravenous high-dose acyclovir for varicella; consideration of prophylactic antibiotic therapy and/or immunoglobulin replacement therapy; physiotherapy and acute and long-term medical management for bronchiectasis. Recurrent severe infections and/or the presence of severe combined immunodeficiency (SCID) and/or severely depressed erythropoiesis may warrant bone marrow transplantation. * Malignancies. Treat in the usual manner. Prevention of secondary complications: If cervical spinal instability is identified in a person with AD, special care is required during general anesthesia. Surveillance: * Skeletal dysplasia. Clinical and (if warranted) radiographic monitoring of growth, joints of the lower extremities, and spine annually in childhood and as required in adulthood. Individuals with AD require annual clinical and radiographic monitoring of the spine. * Anemia. For those who have not had anemia, observe for clinical signs of anemia; for those in remission after treatment, monitor for evidence of relapse. * Immunodeficiency/infection. Monitor all children regardless of immune status during the first two years of life for recurrent infections, especially life-threatening varicella. Annual evaluation after age two years. High-resolution CT examination for those with features suggestive of bronchiectasis. * Malignancies. No specific recommendations exist; regular examination for evidence of lymphomas, basal cell carcinomas, and other associated malignancies is advised. * Endocrinology. Monitor pubertal maturation. Agents/circumstances to avoid: Administration of live vaccines when signs of abnormal immunologic function or SCID are present. Evaluation of relatives at risk: Early diagnosis of relatives at risk for the CHH-AD spectrum allows for early management of manifestations that can be associated with significant morbidity (e.g., infections, immunization with live vaccines, malignancies). ### Genetic counseling. The CHH-AD spectrum is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier of a pathogenic variant, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified. ## Diagnosis There are no formal diagnostic criteria for CHH, as individuals present with highly variable phenotypes. The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum ranging from short stature without hypotrichosis with only radiographic evidence of metaphyseal dysplasia (MDWH) [Bonafé et al 2002] to short stature with hypotrichosis and variable metaphyseal dysplasia of the tubular bones (CHH) [McKusick et al 1965, Mäkitie & Kaitila 1993] to severe deforming short stature with metaphyseal, epiphyseal, and vertebral dysplasia (anauxetic dysplasia [AD]) [Horn et al 2001, Thiel et al 2005]. Newborn screening for severe combined immunodeficiency using detection of T-cell receptor excision circles is able to identify some of the individuals with CHH prior to recognition of other findings [Kwan et al 2013]. ### Suggestive Findings CHH-AD spectrum disorders should be suspected in individuals with: * Mild to severe disproportionate short-limbed short stature (final adult height <85-151 cm) * Presence of variable metaphyseal dysplasia with epiphyseal and vertebral dysplasia in the severe end of the spectrum Especially when accompanied by: * Short tubular bones * Bowed femora and tibiae * "Bullet"-shaped middle phalanges, cone-shaped epiphyses, and premature epiphyseal fusion on hand radiographs * Laxity of ligaments with joint hypermobility, but limited extension of the elbows * Fine, silky hair * Increased rate of infections or intestinal dysfunction or anemia #### Clinical Findings by Phenotype Cartilage-hair hypoplasia (CHH) * Disproportionate short-limb short stature (present in 100% of affected adults; prenatal onset in 76%-93%) * Short fingers and toes * Bowed femora and tibiae (present in 77%) * Laxity of ligaments with hypermobility of joints (87%) * Limited extension of the elbows (83%) * Lumbar lordosis, chest deformity (~50%) * Blonde, sparse, fine silky hair (89%-93%) * Impaired lymphocyte proliferation and T-lymphocyte function (88%) with increased rate of: * Infections in infancy and childhood (35%-65%) * Severe varicella infection (11%) * Severe combined immunodeficiency * Bronchiectasis (29%) [Kostjukovits et al 2017a] * Macrocytic, hypoplastic anemia in early childhood (79%) * Lymphomas; leukemia; neoplasms of the skin, eye, and liver (6%-11%) * Congenital megacolon or Hirschsprung disease (7%-8%) * Intestinal malabsorption with diarrhea and failure to thrive * Cutaneous and visceral granulomas [Moshous et al 2011, McCann et al 2014] Metaphyseal dysplasia without hypotrichosis (MDWH) * Clinical features similar to CHH, but with normal hair * Absence of immunodeficiency, anemia, and intestinal manifestations Anauxetic dysplasia (AD) * Prenatal onset of extreme short-limb short stature (100%) * Barrel chest with hyperlordosis and kyphoscoliosis * Dislocated hips * Atlantoaxial subluxation leading to cervical spine compression * Facial features. Midfacial hypoplasia and macroglossia * Dental abnormalities * Mild intellectual disability #### Radiographic Findings by Phenotype Note: Radiographic findings tend to be highly variable. Cartilage-hair hypoplasia (CHH) * Short and thick tubular bones * Short and bullet-shaped metacarpals and phalanges with cone-shaped epiphyses * Metaphyseal dysplasia of all tubular bones, most prominent changes at the knees * Distal metaphyses. Wide, flared, occasionally scalloped with cystic areas; poor ossification with trabeculation * Epiphyseal changes. Absent or mild in the femoral head * Vertebral bodies. Normal or mild biconvexity with increased height, lumbar lordosis, reduced widening of interpediculate distance in the lumbar spine Metaphyseal dysplasia without hypotrichosis (MDWH). Similar to those in CHH Anauxetic dysplasia (AD) * Vertebral bodies. Late-maturing ovoid with concave dorsal surfaces in the lumbar region; dislocation in the cervical spine * Femora. Small capital femoral epiphyses with hypoplastic femoral necks * Iliac bodies. Hypoplastic * Acetabulae. Shallow * Metacarpals. Short with widened shafts (I and V) * Phalanges. Very short and broad with small, late ossifying epiphyses and bullet-shaped middle phalanges ### Establishing the Diagnosis The diagnosis of CHH-AD is established in a proband with the above Suggestive Findings including clinical and characteristic radiographic findings. If clinical and radiographic findings are inconclusive, identification of biallelic pathogenic variants in RMRP by molecular genetic testing (see Table 1) can confirm the diagnosis and allow for family studies. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of CHH-AD is broad, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with short stature and/or immune deficiency are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic and laboratory findings suggest the diagnosis of CHH-AD molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of RMRP detects nucleotide variants and small intragenic deletions/insertions/duplications; typically, heterozygous whole-gene deletions/duplications are not detected. Perform sequence analysis first. Sequence analysis should cover both the transcribed region and the promoter region. If only one or no pathogenic variant is found perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Targeted analysis for the common g.70A>G pathogenic variant can be performed first in individuals of Finnish or Amish ancestry. Note: This noncoding RNA spans only 268 bp; therefore, targeted testing by sequence analysis is likely to result in analysis of the entire gene. * A multigene panel that includes RMRP and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the phenotype is indistinguishable from many other inherited disorders characterized by short stature, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used, but genome sequencing is also possible; however, regardless of the method, RMRP pathogenic variants may not be detected because RMRP is a small (268-bp) untranslated gene without introns and exons. Note that although exome sequencing is defined traditionally as the sequence encompassing all exons of protein-coding genes in the genome it also may be extended to target functional non-protein-coding elements such as RMRP. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in CHH-AD Spectrum Disorders View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method RMRPSequence analysis 3~100% 4 Gene-targeted deletion/duplication analysis 5None reported 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include nucleotide substitution and small intragenic deletions. Typically, whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 4\. Martin & Li [2007] 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. To date, no large deletions or duplications involving RMRP have been reported to cause CHH-AD spectrum disorders [Ridanpää et al 2001, Thiel & Rauch 2011]. ## Clinical Characteristics ### Clinical Description Cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes three phenotypes: * Metaphyseal dysplasia without hypotrichosis (MDWH); * Cartilage-hair hypoplasia (CHH), with metaphyseal dysplasia and hypotrichosis; and * At the severe end, the rare anauxetic dysplasia (AD), with the most pronounced skeletal phenotype. The mechanisms for phenotypic variability are incompletely understood (see Genotype-Phenotype Correlations). Disproportionate short-limb short stature is the hallmark finding and is usually recognized in the newborn and occasionally prenatally. Proportionate short stature has been observed in some individuals [van der Burgt et al 1991, Mäkitie & Kaitila 1993]. Normal growth in childhood has also been reported [Klemetti et al 2017]. Growth failure is progressive and associated with the degree of disproportion. Lumbar lordosis and scoliosis may contribute to the short stature. Marked inter- and intrafamilial variability of short stature has been observed. Growth curves for Finnish individuals with CHH have been published. Final adult height ranges from 104 to 151 cm in CHH (median: 131 cm in males; 122 cm in females) and less than 85 cm in AD [Mäkitie et al 1992a, Mäkitie & Kaitila 1993, Horn et al 2001]. Laxity of ligaments with joint hypermobility is marked especially in the hands and feet. The laxity of lateral ligaments of the knees contributes to the varus deformity of the lower extremities. Fine silky hair. Sparse hair, reduction of the diameter of the hair shaft, and loss of the central pigmented core of the hair shaft contribute to the distinctive appearance of the hair. About 15% of affected persons have complete primary alopecia including scalp hair and eyelashes, eyebrows, and body hair. Immunodeficiency may manifest as lymphopenia and defects in T-lymphocyte function and/or proliferation [Kavadas et al 2008]. Sometimes defects in B-lymphocyte proliferation with low IgG and undetectable IgA are observed. Although deficient cellular immunity is present in most affected individuals (88%), an increased rate of infection is noted in only 35%-65%, usually during infancy and childhood. Early reports on fatal varicella infection conflict with the more recent publications on larger cohorts of individuals with CHH with mostly uncomplicated varicella disease [Mäkitie et al 1998]. Severe respiratory disease (e.g., lymphoplasmacytic bronchiolitis) has been reported in children [Bailly-Botuha et al 2008]. Chronic viral infections with bocavirus and norovirus have been reported [Kainulainen et al 2014]. Impaired cellular immunity persists into adulthood. Individuals with CHH and combined immunodeficiency are at particular risk for chronic bronchiectasis [Toiviainen-Salo et al 2008], which may, however, develop even in individuals with mild immunodeficiency [Kostjukovits et al 2017a]. Fatal enteroviral meningoencephalitis has been reported in a child with CHH [Vatanavicharn et al 2010]. Autoimmune complications. In rare instances autoimmune complications and a form of severe allergic reaction have been observed in CHH; however, the pathophysiology is still unknown [Bacchetta et al 2009, Narra & Shearer 2009]. Cutaneous and visceral granulomatous inflammatory lesions have been described in five individuals with CHH [Moshous et al 2011, McCann et al 2014]. Individuals with CHH demonstrate broad autoantibody reactivity compared to healthy controls [Biggs et al 2017]. Anemia. Deficient erythropoiesis may lead to mild to severe macrocytic anemia. Mild anemia is seen in about 80% of those with CHH and resolves spontaneously in childhood in most cases [Mäkitie et al 1992b]. Severe and persistent anemia resembling that of Diamond-Blackfan syndrome is seen in about 6% [Williams et al 2005]. About 50%-75% of those with severe anemia require lifelong transfusions or bone marrow transplantation (see Management); on occasion spontaneous resolution is observed [Williams et al 2005]. Malignancies. Extended follow up of persons with CHH revealed that about 11% of the cohort (14/123) followed for 39 years had developed malignancies [Taskinen et al 2008]. Kaplan-Meier estimate gave a probability of a cancer event (excluding basal cell carcinoma) of 41% by age 65 years. Nine of the 14 malignancies were diagnosed in persons age 15-44 years. Of the 14 who developed malignancies, nine have died; median time to death was three months after initial diagnosis of the malignancy. Underlying pathogenic variants in RMRP and severity of preceding immunodeficiency varied and did not correlate with risk of malignancy. The most frequently observed cancers are non-Hodgkin lymphoma, followed by squamous cell carcinoma, leukemia, and Hodgkin lymphoma; non-aggressive basal cell carcinoma was also common. There are isolated reports of uterine carcinoma and vocal cord carcinoma [Kostjukovits et al 2017b]. Rarely, two or more malignancies are observed in one individual. Intestinal problems * Newborn period. Hirschsprung disease with short-segment or total colon aganglionosis is observed in 7%-8% of those with CHH, especially infants with the severe forms of CHH [Mäkitie et al 2001a]. * Infancy. When Hirschsprung disease has been excluded, malabsorption secondary to gastrointestinal infections can occur in the first two years of life [Mäkitie et al 1995]. The main findings are "celiac syndrome" with diarrhea and failure to thrive. Although most intestinal manifestations occur in the first two years of life, they can occur later in childhood. Intestinal problems have not been described in AD or MDWH. Impaired spermatogenesis. Because of a defect in cell proliferation, males with CHH have defects in sperm concentration, motility, morphology, and immunology [Mäkitie et al 2001b]. Testicles are smaller than normal for age and pubertal status; however, serum concentrations of testosterone, inhibin B, and gonadotropins are within the normal range in most individuals. Delayed puberty. Girls with CHH may have hypogonadotropic or normogonadotropic hypogonadism with no spontaneous pubertal development [Holopainen et al 2018]. Additional findings observed in some persons with AD [Horn et al 2001]: * Atlantoaxial subluxation with fatal cervical compression * Mild intellectual disability ### Genotype-Phenotype Correlations The CHH-AD spectrum includes a range of phenotypes. RMRP is not translated into a protein; thus, genotype-phenotype correlation depends on the position of the pathogenic variant in the transcript and the proposed effect on transcript folding and RNA/protein interaction (see Molecular Genetics). The milder phenotypes are usually caused by either of the following: * Compound heterozygous or homozygous pathogenic variants within the transcript resulting in little to intermediate effect on function of the RNase MRP (complex formed of the RMRP transcript and other proteins) * Compound heterozygosity for one pathogenic variant within the transcript and one pathogenic variant in the promoter region AD is caused by either of the following: * Compound heterozygous or homozygous biallelic pathogenic variants that severely alter function OR * Compound heterozygosity for: * One pathogenic variant within the transcript that severely alters the RNase MRP function AND * A hypomorphic (reduced function) allele (e.g., pathogenic variant leading to an unstable transcript) ### Nomenclature Cartilage hair hypoplasia (CHH) or metaphyseal chondrodysplasia, McKusick type was first described in the Old Order Amish population by McKusick and his colleagues [McKusick et al 1965]. Individuals with normal hair and metaphyseal dysplasia, called metaphyseal dysplasia without hypotrichosis (MDWH), were reported by Bonafé et al [2002]. Anauxetic dysplasia was named after the Greek "not to permit growth" [Horn et al 2001]. ### Prevalence About 700 individuals are currently known to have a CHH-AD spectrum disorder [Kaitila, personal communication]. The most severe form, AD, is extremely rare: fewer than ten affected individuals have been reported. Affected individuals have been reported in most populations; however, a high incidence of CHH was noted in the Old Order Amish population with a prevalence of 1:1,000-2:1,000 (carrier frequency 1:10) and in Finland with an incidence of 1:23,000 (carrier frequency 1:76) [Mäkitie 1992, Mäkitie & Kaitila 1993]. ## Differential Diagnosis ### Table 2. Disorders to Consider in the Differential Diagnosis of Cartilage-Hair Hypoplasia – Anauxetic Dysplasia (CHH-AD) Spectrum Disorders View in own window Differential Diagnosis DisorderGene(s)MOIClinical Features OverlappingDistinguishing Anauxetic dysplasia 2 (OMIM 617396)POP1AR * Short stature & metaphyseal dysplasia * ↓ peripheral blood mononuclear cell proliferation ability 1 In anauxetic dysplasia 2: no clinical symptoms of immunodeficiency Anauxetic dysplasia 3 (OMIM 618853)NEPROAR * Short stature& metaphyseal dysplasia * Hair hypoplasia 2 In anauxetic dysplasia 3: no clinical symptoms or laboratory signs of immunodeficiency Schmid dysplasiaCOL10A1ADShort stature & radiographic metaphyseal abnormalities (metaphyseal dysplasia especially in proximal femur) resembling CHHIn Schmid dysplasia: no extraskeletal manifestations Jansen dysplasia (OMIM 156400)PTH1RADShort stature & radiographic metaphyseal abnormalities resembling CHHIn Jansen dysplasia: hypercalcemia & hypercalciuria 3 Shwachman-Diamond syndrome (SDS)SBDSAR * Short stature & radiographic metaphyseal abnormalities resembling CHH * ↑ infections * Anemia In SDS: * Milder skeletal features (usually) * Principal manifestations: exocrine pancreatic insufficiency, neutropenia, & failure to thrive 4 Schimke immunoosseous dysplasia (SIOD)SMARCAL1AR * Short stature * Cellular immune deficiency 5 In SIOD: * Short stature caused by short trunk (vs short-limbed short stature in CHH-AD) * Characteristic facies * Vascular problems Combined immunodeficiency syndromesSee footnote 6.AD AR XLImmunodeficiencyIn most immunodeficiency syndromes: no skeletal abnormalities Omenn syndrome (OMIM 603554)RAG1 RAG2 DCLRE1CAR * Short stature * Hematologic changes * Immunologic changes Omenn syndrome is more severe & incls: * Ichthyosiform skin changes * Septicemia Isolated congenital neutropenia (See ELANE-Related Neutropenia.)See footnote 8.AD AR XLCongenital neutropeniaSkeletal phenotype in CHH Syndromic congenital neutropenia 7 (See WAS-Related Disorders, G6PC3 Deficiency.) AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked 1\. Glazov et al [2011] 2\. Narayanan et al [2019] 3\. Savoldi et al [2013] 4\. Levin et al [2015] 5\. If recurrent infections are present, milder forms of SIOD may be confused with CHH [Baradaran-Heravi et al 2008]. 6\. See OMIM Phenotypic series: Immunodeficiency (Select Examples) - PS300755 for genes associated with this phenotype in OMIM. 7\. Congenital neutropenia that occurs as part of a syndrome can be caused by pathogenic variants affecting glucose metabolism or lysosomal function. 8\. See OMIM Phenotypic series: Neutropenia, severe congenital - PS202700 for genes associated with this phenotype in OMIM. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with a cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorder, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended: ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with CHH-AD Spectrum Disorder View in own window System/ConcernEvaluationComment RespiratoryPulmonary consultationEval for evidence of respiratory disease Gastrointestinal/ FeedingGastroenterologic consultationEval for congenital megacolon if clinical observation is suggestive MusculoskeletalFull skeletal surveyTo incl (in AD) views of cervical spine to identify cervical vertebral abnormalities & assess risk for atlantoaxial subluxation Orthopedic consultationEval for complications of joint laxity, lumbar lordosis, chest deformity, scoliosis, & varus deformity of lower extremities Hematologic/ LymphaticComplete blood count w/differential cell countEval for macrocytic anemia & immunodeficiency 1 Hematologic consultationIf blood count is abnormal, for further assessment & treatment Allergic/ ImmunologicLaboratory evals for immunodeficiency 1To incl: * Serum concentration IgG, IgA, IgM, & IgG subclasses * CD3, 4, 8, 19, 16/56 * Post-vaccine titers * Other immunologic parameters: * Allogeneic lymphocyte cytotoxicity * TREC analysis * T-cell repertoire * Proliferation response to PHA * Proliferation response to anti-CD3 Immunologic consultationIf immunologic testing is abnormal or if child has infections, for assessment & treatment & to determine vaccination program & approach to varicella prophylaxis Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselor AD = anauxetic dysplasia; TREC = T-cell receptor excision circles 1\. Rider et al [2009] ### Treatment of Manifestations Skeletal dysplasia * Corrective osteotomies may be warranted in late childhood or adolescence for excessive varus deformity of the lower extremities [Riley et al 2015]. * In persons with AD, surgery may be needed to fuse malformed cervical vertebrae in infancy and to correct or prevent the progression of kyphoscoliosis. * Orthopedic surgery may be complicated by low bone density. Short stature. Treatment with recombinant growth hormone has not shown any sustained benefit in individuals with CHH and cannot be recommended [Obara-Moszynska et al 2013]. Immunodeficiency and infection. The treatment of infections in individuals with immunodeficiency is based on their type, location, and severity. * Immediate antiviral treatment with intravenous high-dose acyclovir must be considered at the first symptoms of varicella infection to prevent complications. * Consider prophylactic antibiotic therapy if the individual has recurrent infections or if neutropenia/severe lymphopenia is present. Consider also immunoglobulin replacement therapy if immunoglobulin or IgG subclass levels are low, or if vaccine responses are inadequate. * Individuals with bronchiectasis need proper management of infectious exacerbations and physiotherapy. Consider also long-term treatment with inhaled antibiotics or oral macrolide [Altenburg et al 2015]. * Recurrent severe infections and/or the presence of severe combined immunodeficiency (SCID) may warrant bone marrow transplantation / hematopoietic stem cell transplantation (HSCT) [Guggenheim et al 2006]. HSCT has resulted in normalization of T-lymphocyte numbers and function, resolution of autoimmune manifestations, and catch-up growth, probably due to reduced infections. Overall survival rates have been reported at 63% for unrelated donor transplants and as high as 80% for matched sibs. HSCT should be considered in selected individuals with CHH with recurrent infections and autoimmune manifestations or bone marrow dysplasia for whom a well-matched donor is available [Bordon et al 2010]. * Anti-TNFa therapy has been used successfully in the treatment of cutaneous and visceral granulomas. However, fatal progressive multifocal leukoencephalopathy caused by JC virus has been described during treatment with anti-TNFa antibodies. HSCT resulted in disappearance of granulomas in two of three transplanted individuals [Moshous et al 2011]. Anemia * Treatment of severe anemia secondary to depressed erythropoiesis may require repeated red cell transfusions in infancy and childhood; lifelong transfusions or bone marrow transplantation are rarely needed [Williams et al 2005]. In individuals requiring repeated transfusions iron chelation is successful and well tolerated when needed [Taskinen et al 2013]. * Although steroid treatment has been effective in treating anemia in some persons with CHH, the available data are not sufficient to recommend this therapy in general, especially considering the potential side effects of immune suppression and growth retardation. Malignancy. No specific recommendations for the treatment of the observed malignancies are available. Non-Hodgkin lymphoma often has a poor prognosis with conventional cytotoxic protocols [Taskinen et al 2008]. Endocrine. Pubertal maturation may be delayed and may require hormonal induction. ### Prevention of Secondary Complications If a cervical spine abnormality and/or instability is identified, special care should be exercised when general anesthesia is administered. ### Surveillance Skeletal dysplasia * Children with CHH require annual measurement of linear growth and body proportions; comparison with published disease-specific growth curves [Mäkitie et al 1992a] is helpful. * Pubertal development should be monitored during annual follow-up visits and hypogonadism excluded if puberty is significantly delayed. * Clinical assessment for deformities of the lower extremities and joints is appropriate. Radiographic evaluation and orthopedic consultation is necessary if symptomatic misalignment, restricted knee or hip mobility, or symptomatic joint laxity is present. * Individuals with AD require annual clinical and radiographic monitoring of the spine. Immunodeficiency and infection * As no clinical parameters predict susceptibility to infection in children, ongoing follow up by physicians with experience in this condition is recommended, including routine physical examination and laboratory testing for early detection of infection. * Particularly in the first two years of life, children with normal initial immunologic assessment should be monitored for recurrent infections, especially life-threatening varicella infections [Notarangelo et al 2008, Rider et al 2009]. * Laboratory markers for immunodeficiency may fluctuate in children with CHH, thus emphasizing the need for regular yearly follow up [Kainulainen et al 2014]. * Bronchiectasis should be suspected especially in subjects with frequent respiratory tract infections and combined immunodeficiency; high-resolution computed tomography should be used for diagnosis [Toiviainen-Salo et al 2008]; lung MR examination is recommended for follow up [Kostjukovits et al 2017a]. Anemia * Observe for clinical signs of anemia starting from the time of the initial diagnosis until early adolescence. * Follow RBC, hematocrit, and hemoglobin levels in those in remission after treatment for anemia at least every six months or when clinical signs of anemia reappear. Note: (1) No data are available on the likely timing of recurrence of anemia after successful treatment; (2) severe anemia in adolescents and adults with CHH can be the presenting symptom of malignancy and may require extensive investigations with bone marrow evaluation and imaging studies. Malignancy * Children. Although no specific recommendations exist, it is advised that children be evaluated annually by their pediatrician or primary health care provider for lymphomas and other associated malignancies by careful clinical examination and routine blood tests. Skin should be inspected for abnormal changes, lymph nodes for enlargement, and abdomen for hepatomegaly, splenomegaly, or other abnormalities. Abdominal ultrasound is recommended at a regular one- to two-year interval, as well as yearly laboratory tests including blood counts with differential, LDH, and uric acid. * Adults. As no clinical parameters predict susceptibility to malignancy in adults, ongoing regular follow up beyond adolescence is recommended, including routine physical examination and laboratory testing for early detection of malignancy, as described above. The frequency of follow-up visits needs to be determined on an individual basis. Endocrinology. Monitor pubertal maturation. ### Agents/Circumstances to Avoid Routine immunizations with inactivated vaccines are considered safe in persons with CHH. However, immunization with live vaccines should be carefully considered in those with CHH and evidence of abnormal immunologic function, and should be avoided in those with CHH and SCID [Rider et al 2009]. ### Evaluation of Relatives at Risk Early diagnosis of relatives (i.e., sibs) at risk for CHH-AD spectrum disorders is important for early recognition and management of manifestations that can be associated with significant morbidity (e.g., infections, immunization with live vaccines, malignancies). Relatives at risk should be tested if clinical features, especially short stature, are present; completely asymptomatic individuals need not be tested. Evaluations can include: * Molecular genetic testing if the pathogenic variants in the family are known; * Radiographic evaluation and RMRP sequence analysis if the pathogenic variants in the family are not known. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management No issues are known; however, experience is limited. ### Therapies Under Investigation Varicella vaccine is being investigated for children with CHH who have not had varicella. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders

None

gene_reviews

https://www.ncbi.nlm.nih.gov/books/NBK84550/

{"synonyms": []}

Adipsia Other nameshypodipsia Molecular structure of vasopressin. This hormone is related to Type A and Type B adipsia. Adipsia, also known as hypodipsia, is a symptom of inappropriately decreased or absent feelings of thirst.[1][2] It involves an increased osmolality or concentration of solute in the urine, which stimulates secretion of antidiuretic hormone (ADH) from the hypothalamus to the kidneys. This causes the person to retain water and ultimately become unable to feel thirst. Due to its rarity, the disorder has not been the subject of many research studies. Adipsia may be seen in conditions such as diabetes insipidus[3] and may result in hypernatremia.[4] It can occur as the result of abnormalities in the hypothalamus, pituitary and corpus callosum,[5] as well as following pituitary/hypothalamic surgery.[6] It is possible for hypothalamic dysfunction, which may result in adipsia, to be present without physical lesions in the hypothalamus, although there are only four reported cases of this.[7] There are also some cases of patients experiencing adipsia due to a psychiatric disease. In these rare psychogenic cases, the patients have normal levels of urine osmolality as well as typical ADH activity.[8] ## Contents * 1 Cause * 1.1 Dopamine * 1.2 Hypothalamus * 2 Diagnosis * 2.1 Symptoms * 2.2 Testing * 2.3 Characteristic * 2.3.1 Type A * 2.3.2 Type B * 2.3.3 Type C * 2.3.4 Type D * 3 Management * 4 See also * 5 References * 6 External links ## Cause[edit] ### Dopamine[edit] Dopamine, a neurotransmitter, has been linked with feeding behaviors. In an experiment, scientists measured how much food and water mice consumed when they were born without dopamine in their systems. They found that without dopamine, the mice would starve and be dehydrated to the point of death. The scientists then injected the mice without dopamine with its precursor, L-DOPA, and the mice started eating again. But, even though the mice were born without dopamine in their systems, they still had the capacity to control their feeding and drinking behaviors, suggesting that dopamine does not play a role in developing those neural circuits. Instead, dopamine is more closely related to the drive for hunger and thirst. Although the lack of dopamine resulted in adipsia in these rats, low levels of dopamine do not necessarily cause adipsia. [9] The Nigrostriatal Pathway (highlighted in blue) is crucial for dopamine production and transmission. Location of the hypothalamus in the brain. Other findings in support of the role of dopamine in thirst regulation involved the nigrostriatal pathway. After completely degenerating the pathway, the animal becomes adipsic, aphagic, and loses its interest in exploring. Although dopamine plays a role in adipsia, there is no research involving exclusively the relationship between adipsia and dopamine, as changes in dopamine simultaneously mediate changes in eating and curiosity, in addition to thirst.[10] ### Hypothalamus[edit] The area of the brain that regulates thirst is located in the anterior part of the hypothalamus. The anterior hypothalamus is in close proximity to osmoreceptors which regulate the secretion of antidiuretic hormone (ADH). ADH secretion is one of the primary mechanisms by which sodium and osmolar homeostasis are regulated, ADH is also secreted when there are small increases in serum osmolality. Thirst is triggered by increases in serum osmolality and along with increases ADH secretion. Both serum osmolality and ADH maintain normal ranges of serum osmolality. Adipsia can tend to result from lesions to hypothalamic regions involved in thirst regulation. These lesions can be congenital, acquired, trauma, or even surgery. Lesions or injuries to those hypothalamic regions cause adipsia because the lesions cause defects in the thirst regulating center which can lead to adipsia. Lesions in that region can also cause adipsia because of the extremely close anatomical proximity of the hypothalamus to ADH-related osmoreceptors.[8] ## Diagnosis[edit] ### Symptoms[edit] Diagnosing adipsia can be difficult as there is no set of concrete physical signs that are adipsia specific. Changes in the brain that are indicative of adipsia include those of hyperpnea, muscle weakness, insomnia, lethargy, and convulsions (although uncommon except in extreme cases of incredibly rapid rehydration). Patients with a history of brain tumors, or congenital malformations, may have hypothalamic lesions, which could be indicative of adipsia.[4] Some adults with Type A adipsia are anorexic in addition to the other symptoms.[11] ### Testing[edit] Initial testing for adipsia involves electrolyte, blood urea nitrogen (BUN) and creatinine levels, serum and urine osmolality, blood hormone levels, like vasopressin (AVP). In patients who have defects in thirst regulation and vasopresin secretion, serum vassopresin levels are low or absent.[12] Measurements of urine electrolytes and osmolality are critical in determining the central, rather than renal, nature of the defect in water homeostasis. In adipsia, the fractional excretion of sodium is less than 1%, unless a coexisting defect in AVP secretion is present. In salt intoxication, the urine sodium concentrations are very high and fractional excretion of sodium is greater than 1%. Initial test results may be suggestive of diabetes insipidus. The circulating AVP levels tend to be high, which indicate an appropriate response of the pituitary to hyperosmolality. Patients may have mild stable elevations of serum sodium concentrations, along with elevations in both BUN and creatinine levels and in the BUN/creatinine ratio.[4] ### Characteristic[edit] #### Type A[edit] Type A (essential hypernatremia syndrome) involves an increase of the level in which solvent molecules can pass through cell membranes (osmotic threshold) for vasopressin release and the activation of the feeling of thirst. This is the most characterized sub-type of adipsia, however there is no known cause for Type A adipsia. There is debate over whether osmoreceptor resetting could lead to the increase in threshold. Other studies have shown that it is the loss of osmoreceptors, not resetting, that cause the change in threshold.[13] Patients with Type A adipsia can be at risk of seizures if they rapidly re-hydrate or quickly add a significant amount of sodium into their bodies. If not treated, Type A adipsia could result in both a decrease in the size of the brain and bleeding in the brain.[11] #### Type B[edit] Type B adipsia occurs when vasopressin responses are at decreased levels in the presence of osmotic stimuli. Although minimal, there is still some secretion of AVP. This type may be due to some elimination of osmoreceptors.[13] #### Type C[edit] Dopamine pathways in the brain. The production of dopamine is concentrated in the Ventral Tegmental Area and the Substantia Nigra. Type C adipsia (type C osmoreceptor dysfunction) involves complete elimination of osmoreceptors, and as a result have no vasopressin release when there normally would be. Type C is generally the adipsia type found in patients with adipsic diabetes insipidus.[13] #### Type D[edit] Type D is the least commonly diagnosed and researched type of adipsia. The AVP release in this subtype occurs with normally functioning levels of osmoregulation.[13] ## Management[edit] People affected by adipsia lack the ability to feel thirst, thus they often must be directed to drink. Adipsic persons may undergo training to learn when it is necessary that they drink water. Currently, there is no medicine available to treat adipsia. For people with adipsia because of hypothalamic damage, there is no surgical or medicinal option to fix the damage. In some cases where adipsia was caused by growths on thirst centers in the brain, surgical removal of the growths was successful in treating adipsia. Although adipsic persons must maintain a strict water intake schedule, their diets and participation in physical activities are not limited. People affected by diabetes insipidus have the option of using the intranasal or oral hormone desmopressin acetate (DDAVP), which is molecularly similar enough to vasopressin to perform its function. In this case, desmopressin helps the kidneys to promote reabsorption of water.[4] Some doctors have reported success in treating psychogenic adipsic patients with electroconvulsive therapy, although the results are mixed and the reason for its success is still unknown.[8] Additionally, some patients who do not successfully complete behavioral therapy may require a nasogastric tube in order to maintain healthy levels of fluids.[8] ## See also[edit] * Polydipsia \- excessive thirst, the opposite of adipsia * Thirst * Osmoregulation ## References[edit] 1. ^ "adipsia | pathology". Encyclopædia Britannica. Retrieved 2016-04-26. 2. ^ Lin, M; Liu, SJ; Lim, IT (August 2005). "Disorders of water imbalance". Emergency Medicine Clinics of North America. 23 (3): 749–70, ix. doi:10.1016/j.emc.2005.03.001. PMID 15982544. 3. ^ Crowley, R. K.; Sherlock, M.; Agha, A.; Smith, D.; Thompson, C. J. (2007). "Clinical insights into adipsic diabetes insipidus: a large case series". Clinical Endocrinology. 66 (4): 475–82. doi:10.1111/j.1365-2265.2007.02754.x. PMID 17371462. 4. ^ a b c d Dharnidharka, V.R.; Langman, C.B. (2014). "Adipsia treatment and management". EMedicine. 5. ^ Kim, Boo Gyoung; Kim, Ka Young; Park, Youn Jeong; Yang, Keun Suk; Kim, Ji Hee; Jung, Hee Chan; Nam, Hee Chul; Kim, Young Ok; Yun, Yu Seon (2012). "A Case of Adipsic Hypernatremia Associated with Anomalous Corpus Callosum in Adult with Mental Retardation". Endocrinology and Metabolism. 27 (3): 232–6. doi:10.3803/EnM.2012.27.3.232. 6. ^ Sherlock, M.; Agha, A.; Crowley, R.; Smith, D.; Thompson, C. J. (2006). "Adipsic diabetes insipidus following pituitary surgery for a macroprolactinoma". Pituitary. 9 (1): 59–64. doi:10.1007/s11102-006-8280-x. PMID 16703410. S2CID 8678093. 7. ^ Hayek, A; Peake, GT (1982). "Hypothalamic adipsia without demonstrable structural lesion". Pediatrics. 70 (2): 275–8. PMID 6808452. 8. ^ a b c d Harrington, C.; Grossman, J.; Richman, K. (2014). "Psychogenic adipsia presenting as acute kidney injury: case report and review of disorders of sodium and water metabolism in psychiatric illness". Psychosomatics. 55 (3): 289–295. doi:10.1016/j.psym.2013.06.013. PMID 24012289. 9. ^ Zhou, Q.Y.; Palmiter, R.D. (1995). "Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic". Cell. 83 (7): 1197–1209. doi:10.1016/0092-8674(95)90145-0. PMID 8548806. 10. ^ Ungerstedt, U. (2014). "Adipsia and Aphagia after 6-Hydroxydopamine induced degeneration of the nigro-striatal dopamine system". Acta Physiologica. 82(S367): 95–122. doi:10.1111/j.1365-201X.1971.tb11001.x. PMID 4332694. 11. ^ a b Braun, Michael; Barstow, Craig; Pyzocha, Natasha (May 1, 2015). "Diagnosis and management of sodium disorders: Hyponatremia and hypernatremia". American Family Physician. 91 (5): 299–307. PMID 25822386. Retrieved April 26, 2016. 12. ^ "Adipsia Workup: Laboratory Studies, Imaging Studies, Other Tests". emedicine.medscape.com. Retrieved 2016-04-10. 13. ^ a b c d Holley, A.D.; Green, S.; Davoren, P. (2007). "Extreme hypernatraemia: a case report and brief review" (PDF). Critical Care and Resuscitation : Journal of the Australasian Academy of Critical Care Medicine. 9 (1): 55–8. PMID 17352668. ## External links[edit] Classification D External resources * eMedicine: article/981022 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Adipsia

c0277967

wikipedia

https://en.wikipedia.org/wiki/Adipsia

{"wikidata": ["Q357522"]}

Congenital dermal sinus Other namesSpinal congenital dermal sinus Vertebral column Congenital dermal sinus is an uncommon form of cranial or spinal dysraphism.[1][2] It occurs in 1 in 2500 live births.[2] It occurs as a dermal indentation, found along the midline of the neuraxis and often presents alongside infection and neurological deficit.[1] Congenital dermal sinus form due to a focal failure of dysjunction between the cutaneous ectoderm and neuroectoderm during the third to eight week of gestation.[1][2][3][4] Typically observed in the lumbar and lumbosacral region, congenital dermal sinus can occur from the nasion and occiput region down.[1][2][3] Early diagnosis and treatment is crucial for cases of congenital dermal sinus. It ensures that neurological condition does not degrade and prevents infection. Diagnosis can be confirmed through the use of advanced neuroimaging to observe the tract and associated lesions. ## Contents * 1 Embryogenesis * 2 Diagnosis * 2.1 Clinical features * 2.1.1 Cutaneous abnormalities * 2.1.2 Infection * 2.1.3 Neurological deficit * 2.2 Imaging * 3 Treatment * 4 Historically * 5 References ## Embryogenesis[edit] During normal development, cutaneous ectoderm separates from neuroectoderm to allow for the insertion of mesoderm.[2] That is, the skin separates from the tissue of the spinal cord to allow proper formation of the vertebral column.[2] In cases of congenital dermal sinus there is a failure in this process, resulting in formation of a persistent connection between the skin and neural tissue.[2] This manifests as a tract extending from the surface of the skin to the spinal cord lined with stratified squamous epithelium, surrounded by dermal and neurological tissue.[2][4] The tract may terminate in the deep fascia, or even make contact with neural elements.[1] Congenital dermal sinus may form at any point along the midline of the neuraxis, however, the majority form in the lumbar and lumbosacral region (41% and 35% of cases respectively).[2] ## Diagnosis[edit] Congenital dermal sinus is often diagnosed in infants and children.[1] Early diagnosis is important in congenital dermal sinus, so that treatment can be provided early, to prevent progression of associated complications.[1][2][3][4] ### Clinical features[edit] There three key hallmarks of congenital dermal sinus: cutaneous abnormalities, infection, and neurological deficits.[citation needed] #### Cutaneous abnormalities[edit] Congenital dermal sinus is a tract from the surface layer of the skin, through the deeper tissues into the cranial or spinal cavity.[1] The skin findings of this tract can include: * Pit along neuraxis[3] * Flat capillary hemangioma[3] * Hypertrichosis[1][2][3] * Skin tag[2] * Abnormal pigmentation[1][2] * Subcutaneous lipoma[1][2][3] * Signs of local infection[1][2][3] #### Infection[edit] The stratified squamous epithelium of the congenital dermal sinus tract can extend to the spinal fascia of the dura mater or all the way to the spinal cord.[3][4] Thus, the congenital dermal sinus forms a point of entry for infection, this can allow for the formation of an abscess.[2][4] Infection can then travel up the spinal cord to result in meningitis, which can be fatal if left untreated.[1][4] #### Neurological deficit[edit] Congenital dermal sinus is often also associated with spinal fluid drainage, intradural cysts and spinal cord tethering; conveying neurological deficit.[3] Neurological deficit can occur due to spinal cord compression from intradural dermoid cyst growth in the epidermis and dermis.[3] Tethered spinal cord can result in gait difficulties and sphincter dysfunction, as well as compressing the spine.[4] Neurological deficits are more likely to occur where diagnosis has not been timely, allowing cysts and or infection.[2][3] ### Imaging[edit] Magnetic Resonance Imaging (MRI) is the preferred tool for diagnostic and preoperative imaging of congenital dermal sinus.[1][2][3][4] MRI allows the neural structures to be observed, visualizing the tract and its anomalies and lesions.[1][2][3][4] For example, exposing tethered cord, inclusion tumors or spinal cord malformations.[2] Observation by X-ray is limited in diagnosis, especially due to immature calcification of infants less than 18 months.[4] X-ray may be used in conjunction with MRI or sonogram images to assist preoperatively.[2] ## Treatment[edit] Treatment of congenital dermal sinus involves complete resection of the tract as well as intradural exploration.[3] Prophylactic surgical removal of the congenital dermal sinus tract is beneficial for the patient, allowing neurological and bladder function to be maintained.[1] Early surgical intervention results decreases the risk of infection and/or tumour progression – factors typically associated with delayed presentation of congenital dermal sinus.[2] ] Intradural exploration is necessary as excision of the entire tract, as well as any of its intradural connections, reduces need for further surgical intervention.[3] The surgical technique involves ‘removing the cutaneous lesion in ellipse’.[3] The tract of the congenital dermal sinus must then be explored and excised, with intradural lesions dissected.[3] If not all epithelial tissue is removed, there is a possibility for the dermoid cyst to reoccur and require further operation.[3] Further operations are limited by postoperative and post-infection scarring.[3] ## Historically[edit] Prior to pervasive use and availability of advanced methods of neuroimaging, it is possible that the rate of incidence of congenital dermal sinus has been supplemented by the incidence of coccygeal pits.[2][3] Coccygeal pits are distinct from congenital dermal sinus as they are found within the gluteal cleft, rather than above the gluteal cleft.[2][3] The caudally orientated coccygeal pits are not associated with intradural pathology and do not need to be excised, unlike the cephalically oriented tracts of the congenital dermal sinus which confer great intradural pathology and require surgical intervention.[2][3] While coccygeal pits occur in 4% of neonate population, congenital dermal sinus is only found in 1 in 2500 live births.[2][3] ## References[edit] 1. ^ a b c d e f g h i j k l m n o p Wang, YM; Chuang, MJ; Cheng, MH (September 2011). "Infected spinal dermal sinus tract with meningitis: a case report" (PDF). Acta Neurologica Taiwanica. 20 (3): 188–91. PMID 22009122. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Ackerman, LL; Menezes, AH (September 2003). "Spinal congenital dermal sinuses: a 30-year experience". Pediatrics. 112 (3 Pt 1): 641–7. PMID 12949296. 3. ^ a b c d e f g h i j k l m n o p q r s t u v w x Elton, S; Oakes, JW (January 2001). "Dermal sinus tracts of the spine". Neurosurgical Focus. 10 (1): 1–4. doi:10.3171/foc.2001.10.1.5. 4. ^ a b c d e f g h i j Jindal, A; Mahapatra, AK (September 2001). "Spinal congenital dermal sinus: an experience of 23 cases over 7 years". Neurology India. 49 (3): 243–6. 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Congenital dermal sinus

c0011599

wikipedia

https://en.wikipedia.org/wiki/Congenital_dermal_sinus

{"mesh": ["D016136"], "umls": ["C0011599"], "wikidata": ["Q18612558"]}

## Summary ### Clinical characteristics. Deficiency of argininosuccinate lyase (ASL), the enzyme that cleaves argininosuccinic acid to produce arginine and fumarate in the fourth step of the urea cycle, may present as a severe neonatal-onset form and a late-onset form: * The severe neonatal-onset form is characterized by hyperammonemia within the first few days after birth that can manifest as increasing lethargy, somnolence, refusal to feed, vomiting, tachypnea, and respiratory alkalosis. Absence of treatment leads to worsening lethargy, seizures, coma, and even death. * In contrast, the manifestations of late-onset form range from episodic hyperammonemia triggered by acute infection or stress to cognitive impairment, behavioral abnormalities, and/or learning disabilities in the absence of any documented episodes of hyperammonemia. Manifestations of ASL deficiency (ASLD) that appear to be unrelated to the severity or duration of hyperammonemic episodes: * Neurocognitive deficiencies (attention-deficit/hyperactivity disorder, developmental delay, seizures, and learning disability) * Liver disease (hepatitis, cirrhosis) * Trichorrhexis nodosa (coarse brittle hair that breaks easily) * Systemic hypertension ### Diagnosis/testing. Elevated plasma ammonia concentration (>100 µmol/L), elevated plasma citrulline concentration (usually 100-300 µmol/L), and elevated argininosuccinic acid in the plasma or urine establish the diagnosis of ASLD. Identification of biallelic pathogenic variants in ASL by molecular genetic testing or – in limited instances – by significantly reduced ASL enzyme activity from skin fibroblasts, red blood cells, or in a flash-frozen sample from a liver biopsy help in confirmation of the diagnosis. Note: All 50 states in the US include ASL deficiency in their newborn screening programs. ### Management. Treatment of manifestations: Treatment involves rapid control of hyperammonemia during metabolic decompensations and long-term management to help prevent episodes of hyperammonemia and long-term complications. During acute hyperammonemic episodes, oral protein intake is discontinued, oral intake is supplemented with intravenous lipids and/or glucose, and intravenous nitrogen-scavenging therapy is used. If ammonia levels do not normalize, hemodialysis is the next step. Dietary restriction of protein and dietary supplementation with arginine are the mainstays in long-term management; for those not responsive to these measures, oral nitrogen-scavenging therapy can be considered. Orthotopic liver transplantation (OLT) is considered only in patients with recurrent hyperammonemia or metabolic decompensations resistant to conventional medical therapy. Surveillance: Monitoring the concentration of plasma amino acids to identify deficiency of essential amino acids and impending hyperammonemia at intervals depending on age and metabolic status. Agents/circumstances to avoid: Excess protein intake; less than recommended intake of protein; prolonged fasting or starvation; obvious exposure to communicable diseases; valproic acid; intravenous steroids; hepatotoxic drugs (in those with hepatic involvement). Evaluation of relatives at risk: Testing of at-risk sibs (either by molecular genetic testing if the family-specific pathogenic variants are known or by biochemical testing) shortly after birth can reduce morbidity by permitting early diagnosis and treatment of those who are affected. ### Genetic counseling. ASL deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing and preimplantation diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified. ## Diagnosis Argininosuccinate lyase (ASL) is the enzyme that catalyzes the fourth step in the urea cycle, in which argininosuccinic acid is cleaved to produce arginine and fumarate. All 50 states in the US include ASL deficiency in their newborn screening programs. ### Suggestive Findings ASL deficiency (ASLD) should be suspected in infants with a positive newborn screening result and in symptomatic individuals with supportive clinical and laboratory findings. #### Positive Newborn Screening (NBS) Result NBS for ASL deficiency is primarily based on quantification of the analyte citrulline on dried blood spots. Citrulline values above the cutoff reported by the screening laboratory are considered positive, but elevation of citrulline can also be seen with citrullinemia type 1, citrin deficiency, and pyruvate carboxylase deficiency; hence, confirmation of the diagnosis of ASL deficiency requires follow-up testing to detect elevated plasma or urine concentration of argininosuccinic acid or its anhydride compounds. If testing supports the likelihood of ASL deficiency, additional testing is required to establish the diagnosis (see Establishing the Diagnosis). #### Clinical Findings Individuals with ASLD may present with the following nonspecific supportive clinical features and preliminary laboratory findings that vary by age. In the neonatal period * Hyperammonemia can manifest as increasing lethargy, somnolence, refusal to feed, vomiting, tachypnea, and respiratory alkalosis. * The presentation is typically indistinguishable from that of other proximal urea cycle disorders (i.e., carbamoyl-phosphate synthetase I deficiency, ornithine transcarbamylase deficiency, and citrullinemia type I). In individuals outside the neonatal period * Episodic hyperammonemia that is triggered by acute infection, stress, or non-compliance with dietary restrictions or medications * Liver involvement including hepatomegaly, elevated transaminases, liver fibrosis, or cirrhosis * Neurocognitive deficits such as ADHD, developmental delay, learning disability, and seizures that may be independent of hyperammonemia * Trichorrhexis nodosa consisting of coarse and brittle hair that breaks easily. See images. * Hypertension that may occur in late childhood and adolescence, in the absence of secondary causes * Hypokalemia of unknown etiology that may be chronic and secondary to excess urinary loss of potassium #### Laboratory Findings Plasma ammonia concentration * In the severe forms of ASL deficiency, the initial plasma ammonia concentration (before treatment) may be greater than 1,000 µmol/L, though typically elevations are in the ranges of few hundred µmol/L. * In the milder neonatal and late-onset forms of ASL deficiency, the elevations of plasma ammonia concentration may be less pronounced but above the upper limits of normal for age (see Table 1). ### Table 1. Upper Limits of Normal Plasma Ammonia Concentration by Age View in own window AgeUpper Limits of Normal Ammonia Concentration (µmol/L) 1 0-7 days94 8-30 days80 1-12 months47 1-15 years48 >16 years26 1\. The values depicted are only representative of the normal ranges; the normal reference ranges of individual laboratories should be used for clinical interpretation. Plasma quantitative amino acid analysis. See Table 2. The typical range of citrulline at presentation is 100-300 µmol/L [Brusilow & Horwich 2001]. The typical plasma levels of argininosuccinic acid are between 5 and 110 µmol/L [Ficicioglu et al 2009]. ### Table 2. Age-Related Plasma Amino Acid Concentrations in ASL Deficiency View in own window MetaboliteNormal Plasma Levels Age <2 Years (µmol/L) 1Normal Plasma Levels Age 2-18 Years (µmol/L) 1In ASL Deficiency Citrulline2-416-38Elevated Argininosuccinic acid0-10-1Elevated 2 Arginine42-13218-127Low to normal Glycine104-34492-346Normal to high Glutamine238-842266-746Normal to high Alanine148-420103-528Normal to high 1\. The values depicted are only representative of the normal ranges; the normal references of individual laboratories should be used for clinical interpretation. 2\. The argininosuccinate chromatographic peak may co-elute with leucine or isoleucine, resulting in an apparent increase in one of these two amino acids. The anhydrides that elute later in the run allow for the correct identification of argininosuccinate. Urinary analysis * Orotic acid excretion is typically normal (0.3-2.8 mmol/mol of creatinine); however, orotic aciduria may be observed [Gerrits et al 1993, Brosnan & Brosnan 2007]. * Argininosuccinic acid is significantly elevated. Urinary concentration of argininosuccinate is typically greater than 10,000 µmol/g of creatinine on urine amino acid analysis [Ficicioglu et al 2009] (normal range 0-1 µmol/L). ### Establishing the Diagnosis The diagnosis of ASL deficiency is established in a proband with suggestive metabolic/biochemical findings and confirmed by the following set of specific laboratory test findings: * Elevated plasma ammonia concentration * Elevated plasma citrulline concentration (usually 100-300 µmol/L) * Elevated argininosuccinic acid in the plasma or urine Identification of biallelic pathogenic variants in ASL by molecular genetic testing (Table 3) or – in limited instances – by significantly reduced ASL enzyme activity from skin fibroblasts or red blood cells or in a flash-frozen sample from a liver biopsy help in confirmation of the diagnosis. As the laboratories that can assess enzymatic activity are limited and as molecular genetic testing has become widely available, the latter modality has become the more commonly used confirmatory test for ASL deficiency. Molecular genetic testing approaches, which depend on the clinical findings, can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (typically exome sequencing and exome array). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Children with the distinctive laboratory findings of ASL deficiency described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas symptomatic individuals with nonspecific supportive clinical and laboratory findings (who have not undergone NBS or who had normal NBS results in the past) in whom the diagnosis of ASL deficiency has not been considered are more likely to be diagnosed using comprehensive genomic testing (see Option 2). #### Option 1 When NBS results and other laboratory findings suggest the diagnosis of ASL deficiency, molecular genetic testing approaches can include single-gene testing or use of a multigene panel. Single-gene testing. Sequence analysis of ASL detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If only one or no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Note: Single-gene testing is most appropriate when the diagnosis is made based on results of biochemical testing that show elevated levels of argininosuccinic acid in the plasma or urine. A multigene panel that includes ASL and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see Table 1). Note: A multigene panel test may be considered first when the presentation is with hyperammonemia and confirmatory biochemical diagnosis has not been performed or is unavailable. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When an individual presents with hyperammonemia and confirmatory biochemical diagnosis has not been performed or is unavailable, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 3. Molecular Genetic Testing Used in Argininosuccinate Lyase Deficiency View in own window Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method 3 ASLSequence analysis 4>90% Gene-targeted deletion/duplication analysis 5Unknown 6 1\. See Table A. Genes and Databases for chromosome locus and protein. 2\. See Molecular Genetics for information on allelic variants detected in this gene. 3\. Author observation 4\. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here. 5\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 6\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description The clinical presentation of argininosuccinate lyase deficiency (ASLD) is variable. The two most common forms are severe neonatal-onset form and late-onset form. Severe neonatal-onset form. The clinical presentation of the severe neonatal-onset form, which is indistinguishable from that of other urea cycle disorders, is characterized by hyperammonemia within the first few days after birth. Newborns typically appear healthy for the first 24 hours but within the next few days develop vomiting, lethargy, and refusal to accept feeds [Brusilow & Horwich 2001]. Tachypnea and respiratory alkalosis are early findings. Failure to recognize and treat the defect in ureagenesis leads to worsening lethargy, seizures, coma, and even death. The findings of hepatomegaly and trichorrhexis nodosa (coarse and friable hair) at this early stage are the only clinical findings that may suggest the diagnosis of ASL deficiency [Brusilow & Horwich 2001]. Late-onset form. In contrast to the neonatal-onset form, the manifestations of the late-onset form range from episodic hyperammonemia (triggered by acute infection, stress, or non-compliance with dietary and/or medication recommendations) to cognitive impairment, behavioral abnormalities, and/or learning disabilities in the absence of any documented episodes of hyperammonemia [Brusilow & Horwich 2001]. Whereas manifestations secondary to hyperammonemia are common to all urea cycle disorders, many individuals with ASL deficiency can present with a complex clinical phenotype. The incidence of (1) neurocognitive deficiencies; (2) hepatitis, cirrhosis; (3) trichorrhexis nodosa; and (4) systemic hypertension are overrepresented in individuals with ASL deficiency [Nagamani et al 2012a, Kölker et al 2015, Kho et al 2018]. These manifestations may be unrelated to the severity or duration of hyperammonemic episodes [Saudubray et al 1999, Mori et al 2002, Ficicioglu et al 2009]. #### Complications of ASL Deficiency Neurocognitive deficiencies. In a cross-sectional study of individuals with a urea cycle disorder (UCD), it was observed that persons with ASL deficiency had a higher incidence of developmental delay and neurologic abnormalities than did individuals with OTC deficiency [Tuchman et al 2008]. Individuals with ASL deficiency also had an increased incidence of attention-deficit/hyperactivity disorder (ADHD), developmental delay (intellectual disability, behavioral abnormalities, and/or learning disability), and seizures compared to persons with all other UCDs [Tuchman et al 2008]. In a recent retrospective study, developmental delay and epilepsy were observed in 92% (48/52) and 42% (22/52) of individuals, respectively [Baruteau et al 2017]. Though neurocognitive deficits are common in ASL deficiency, they are not universally present; many individuals with ASL deficiency who are treated with protein restriction and supplemental arginine have normal cognition and development [Widhalm et al 1992, Ficicioglu et al 2009]. The increasing reliance on newborn screening programs for early diagnosis of ASL deficiency allows the evaluation of early treatment on disease progression, especially in the late-onset form: * Ficicioglu et al [2009] reported the long-term outcome of 13 infants diagnosed between age four and six weeks by newborn screening programs. All had low ASL enzyme activity; in spite of optimal therapy with protein restriction and arginine supplementation, four of 13 had learning disability, three had mild developmental delay, three had seizures, and six had an abnormal EEG including abnormal sharp irregular background activity, frequent bilateral paroxysms, and increased slow wave activity. * In a separate cohort of 17 individuals with ASL deficiency diagnosed by newborn screening in Austria, IQ was average or above average in 11 (65%), low average in five (29%), and in the mild intellectual disability range in one (6%). Four had an abnormal EEG without evidence of clinical seizures [Mercimek-Mahmutoglu et al 2010]. The overall favorable outcomes in persons in this cohort may be attributable not only to early dietary and therapeutic interventions but also to the high proportion of persons with very mild disease. Liver disease in individuals with ASL deficiency also appears to be independent of the defect in ureagenesis. The spectrum of hepatic involvement ranges from hepatomegaly to elevations of liver enzymes to severe liver fibrosis [Billmeier et al 1974, Mori et al 2002, Tuchman et al 2008]. Liver involvement has been noted even in individuals treated with protein restriction and arginine supplementation who had not experienced significant hyperammonemia [Mori et al 2002, Mercimek-Mahmutoglu et al 2010]. In a recent retrospective study, hepatomegaly and elevated alanine aminotransferase (ALT) were observed in nearly half of individuals with ASL deficiency [Baruteau et al 2017]. At present no biochemical or molecular features help predict liver dysfunction in people with ASL deficiency. Given the potential direct toxicity of argininosuccinate on hepatocytes, lowering of the argininosuccinate levels in plasma (a reflection of its production by the liver) may have potential benefit [Nagamani et al 2012c]. Trichorrhexis nodosa (see images) is characterized by nodular swellings of the hair shaft accompanied by frayed fibers and loss of cuticle. About half of individuals with ASL deficiency have an abnormality of the hair manifest as dull, brittle hair surrounded by areas of partial alopecia [Fichtel et al 2007]. Normal hair contains 10.5% arginine by weight; hair that is deficient in arginine as a result of ASL deficiency is weak and tends to break. Thus, this clinical feature responds to arginine treatment. Hypertension. Whereas there have only been anecdotal reports of hypertension in ASL deficiency, preclinical data and systematic analysis of blood pressures from one controlled clinical trial have shown that ASL deficiency can directly result in endothelial dysfunction and hypertension [Kho et al 2018]. Usually no secondary causes of hypertension are detected, suggesting that this finding is related to the tissue-autonomous loss of ASL in the vascular endothelium. Electrolyte imbalances. Some individuals develop electrolyte imbalances such as hypokalemia. The hypokalemia is observed even in individuals who are not treated with sodium phenylbutyrate. The etiology is unclear; increased renal wasting has been suggested. ### Genotype-Phenotype Correlations Data are insufficient to infer any genotype-phenotype correlations. ### Prevalence The estimated prevalence is 1:70,000 to 1:218,000 live births [Brusilow & Horwich 2001, NORD]. However, ASL deficiency is very likely underdiagnosed, making it difficult to assess the true frequency in the general population. ## Differential Diagnosis The severe neonatal-onset form of ASL deficiency shares the phenotype of the typical acute neonatal hyperammonemia displayed by other defects in the first four steps in the urea cycle pathway (see Urea Cycle Disorders Overview). The late-onset form of ASL deficiency shares a later onset with other disorders such as late-onset ornithine transcarbamylase (OTC) deficiency, and late-onset citrullinemia type 1. However, the elevation of argininosuccinate is characteristic and differentiates ASL deficiency from other urea cycle disorders. ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual with argininosuccinate lyase (ASL) deficiency following diagnosis, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to diagnosis) are recommended. ### Table 4. Recommended Evaluations Following Initial Diagnosis of ASL Deficiency View in own window EvaluationComment Consultation w/metabolic physician / biochemical geneticist & specialist metabolic dietitian 1 * Transfer to a specialist center w/experience in management of inherited metabolic diseases (strongly recommended) * Consider a short hospitalization at a center of expertise for inherited metabolic conditions to provide detailed education (natural history, maintenance & emergency treatment, prognosis, & risks for acute crises) for caregivers. * Consultation w/a genetic counselor to understand inheritance of this disorder Neurocognitive assessmentConsider referral to a developmental pediatrician, psychologist, &/or neurologist. Baseline evaluation for evidence of hepatic involvement incl hepatomegaly, hepatitis, & signs of liver failure * Plasma AST, ALT, bilirubin, albumin, PT, & INR * Hepatic ultrasound to monitor for hepatomegaly, fibrosis, & additional complications incl hepatocellular carcinoma * Referral to a hepatologist as required Plotting of systolic & diastolic blood pressure on centile charts based on age & stature Consultation w/clinical geneticist &/or genetic counselor ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = international normalized ratio; PT = prothrombin time 1\. After a new diagnosis of ASL deficiency in a child, the closest hospital and local pediatrician should also be informed. ### Treatment of Manifestations Treatment involves rapid control of hyperammonemia during metabolic decompensations and long-term management to help prevent episodes of hyperammonemia and long-term complications. During acute hyperammonemic episodes severe enough to cause neurologic symptoms, the treatment includes the following [Ahrens et al 2001] (full text) (see Table 5). ### Table 5. Acute Inpatient Treatment in Individuals with ASL Deficiency View in own window Manifestation/ ConcernTreatmentConsideration/Other Acute hyperammonemic episodesDiscontinue oral protein intake. Supplement oral intake w/IV lipids, glucose, & insulin if needed (w/close monitoring of blood glucose) to promote anabolism. IV nitrogen-scavenging therapy. A loading dose of 600 mg/kg L-arginine-HCL & 250 mg/kg each of sodium benzoate & sodium phenylacetate in 25-35 mL/kg of 10% dextrose solution given intravenously over a 90-min period is recommended, followed by a sustained IV infusion of 600 mg/kg L-arginine-HCL & 250 mg/kg each of sodium benzoate & sodium phenylacetate over a 24-hr period.When available, plasma concentrations of ammonia-scavenging drugs should be monitored to avoid toxicity. In the absence of drug levels, a serum anion gap of >15 mEq/L & an anion gap that has risen >6 mEq/L could indicate drug accumulation & ↑risk for toxicity. Failure to decrease ammonia levels w/medical therapyPrompt institution of hemodialysis * Continuous arteriovenous hemodialysis or continuous venovenous hemodialysis w/flow rates >40-60 mL/min is optimal. * Some centers use extracorporeal membrane oxygenation w/hemodialysis. * Although this combination of techniques provides very high flow rates (170-200 mL/min) & rapidly reduces ammonia levels, morbidity is greater because of the need for surgical vascular access. * Nitrogen-scavenging therapy needs to be continued during hemodialysis. * It is the authors' policy to continue nitrogen-scavenging therapy for 12-24 hrs after patient is stabilized & able to accept enteral feeds & medications [Author, personal observation]. HCL = hydrochloride; IV = intravenous Inpatient emergency treatment should: (a) take place at the closest medical facility equipped to treat individuals with metabolic disorders, (b) be started without delay, and (c) be supervised by physicians and specialist dieticians at the responsible metabolic center, who should be contacted without delay. Long-term management. Dietary restriction of protein and dietary supplementation with arginine are the mainstays of long-term management as detailed in Table 6. ### Table 6. Routine Daily Treatment in Individuals with ASL Deficiency View in own window Principle/ ManifestationTreatmentConsideration/Other Dietary restriction of proteinLifelong dietary management is necessary & requires the services of a metabolic nutritionist. 1 * The RDA for dietary protein is higher than the minimum needed for normal growth & hence, most children w/a urea cycle disorder can receive less than the RDA of protein & still maintain adequate growth. * Dietary therapy should be monitored as follows: * Plasma concentrations of ammonia, branched-chain amino acids, & arginine should be maintained w/in normal ranges. * Serum plasma total protein & prealbumin levels should be maintained w/in the low normal ranges. * Plasma glutamine concentration should be maintained at ˂1,000 µmol/L if possible (normal range for individuals ages 2-18 years: 266-746 µmol/L). Arginine base supplementationThe doses of arginine base routinely recommended are 400-700 mg/kg/day in persons weighing ˂20 kg & 8.8-15.4 g/m2/day in those weighing >20 kg. The authors prefer to use a lower dose of arginine whenever possible, in the range of 100-250 mg/kg/day. * Supplementation w/arginine base helps replenish this amino acid (which is deficient in persons w/ASL deficiency) & promote excretion of nitrogen through the urea cycle as argininosuccinate. * Arginine base is preferred for long-term chronic treatment as the chronic use of arginine hydrochloride may lead to hyperchloremic acidosis. * Arginine base supplementation has been shown to reverse the hair changes; however, its efficacy in preventing the chronic complications is not known. While evidence suggests that arginine base supplementation may prevent metabolic decompensations in those w/severe early-onset disease, long-term follow up of persons identified through newborn screening programs did not detect a difference in outcomes between those who were supplemented w/arginine base & those who were not [Batshaw et al 2001, Ficicioglu et al 2009, Mercimek-Mahmutoglu et al 2010]. * As the renal clearance of argininosuccinic acid is high, increasing its production through arginine supplementation effectively increases waste nitrogen disposal, thereby decreasing the risk of hyperammonemia. * However, because of the theoretic risk of argininosuccinic acid toxicity on hepatocytes, reducing the amount of supplemental arginine by initiating nitrogen-scavenging therapy may have merits. The authors prefer to keep the dose of arginine in the range of 100-250 mg/kg/day whenever possible. Oral nitrogen-scavenging therapy (an alternative pathway therapy in which sodium benzoate & phenyl butyrate stimulate the excretion of nitrogen in the form of hippuric acid & phenylacety-lglutamine, respectively)The typical dose ranges 2 for the medications: * Sodium phenylbutyrate, 400-600 mg/kg/day for persons weighing ≤20 kg; 9.9-13 g/m2/day for those weighing >20 kg * Glycerol phenylbutyrate, 4.4-11.2 mL/m2/day * Sodium benzoate, 250-500 mg/kg/day or 5.5 g/m2/day Individuals who have had frequent metabolic decompensations or episodes of ↑ ammonia despite being on a protein-restricted diet & arginine base supplementation are candidates for oral nitrogen-scavenging therapy. Orthotopic liver transplantation (OLT)Recommended only in those w/recurrent hyperammonemia or metabolic decompensations that are resistant to conventional medical therapy, or in those who develop cirrhosis w/associated metabolic decompensations [Author, personal observations]OLT does not correct the arginine deficiency or elevation of argininosuccinic acid at the tissue level, two abnormalities thought to account for the long-term complications of ASL deficiency. Hypertension * Salt restriction & use of antihypertensives indicated in those w/↑ blood pressure. * Antihypertensives may be tried; their efficacy has not been established. HypokalemiaElectrolyte (potassium) supplementation is appropriate when indicated. Neurocognitive delaySpecial educational services & therapies as needed RDA = recommended daily allowance 1\. Some of the correlations between compliance with the prescribed diet and outcome are contradictory. Although in some patients dietary therapy along with arginine supplementation have been shown to reverse the abnormalities of hair, to improve cognitive outcome, and to reverse abnormalities on EEG [Coryell et al 1964, Kvedar et al 1991, Ficicioglu et al 2009], in many dietary therapy has not been shown to influence the outcome of liver disease or cognitive impairment [Mori et al 2002, Mercimek-Mahmutoglu et al 2010]. 2\. The dose ranges depicted are those typically used in individuals with ASLD. The safety and efficacy of phenylbutyrate doses >20 g/day are not known. The dose of glycerol phenylbutyrate depicted is the recommended initial dose in phenylbutyrate-naïve patients. When switching from sodium phenylbutyrate, the total daily dosage of glycerol phenylbutyrate (mL) = total daily dosage of sodium phenylbutyrate (g) x 0.86. The maximal daily dose for benzoate is 12 grams. When prescribing doses in the upper ranges of the recommended dosing, toxicity should be monitored. ### Surveillance ### Table 7. Recommended Surveillance for Individuals with Argininosuccinate Lyase Deficiency View in own window Manifestation/ ConcernEvaluationFrequency/Comment Management of the disorderFollow up in a metabolic clinic w/a qualified metabolic dietician & clinical biochemical geneticistLaboratory & clinical monitoring frequency should depend on metabolic status of the individual. In general: * Neonates: every 2 wks * Infants age 2 mos-1 yr: every 1-3 mos * Children ≥2 yrs: every 3-4 mos Monitor following changes in medical or dietary prescriptions. Abnormal amino acid levelsAnalysis of plasma amino acids to identify deficiency of essential amino acids as well as impending hyperammonemia 1 HypertensionMeasurement of blood pressure using the appropriate-sized cuff & plotting the centile values for age & statureAt each clinic visit Abnormal liver functionLiver function tests (ALT, AST)Every 6-12 mos as required Abnormal electrolytesSerum electrolyte analysisEvery 1-2 yrs as required ALT = alanine aminotransferase; AST = aspartate aminotransferase 1\. Early signs of impending hyperammonemic episodes in older individuals include mood changes, headache, lethargy, nausea, vomiting, refusal to feed, ankle clonus, and elevated plasma concentrations of glutamine, alanine, and glycine. Plasma glutamine concentration may rise 48 hours in advance of increases in plasma ammonia concentration in such individuals. ### Agents/Circumstances to Avoid Avoid the following: * Excess protein intake * Large boluses of protein or amino acids * Less than recommended intake of protein * Prolonged fasting or starvation * Obvious exposure to communicable diseases * Valproic acid * Intravenous steroids * Hepatotoxic drugs in individuals with hepatic involvement ### Evaluation of Relatives at Risk Evaluation of at-risk sibs shortly after birth can reduce morbidity by permitting early diagnosis and treatment of those who are affected. Evaluations can include: * Molecular genetic testing if the pathogenic variant in the family is known; * Plasma amino acids to specifically assess for argininosuccinic acid in a newborn at risk prior to molecular genetic testing or while waiting for molecular genetic testing results. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Therapies Under Investigation Nitrite and nitrate supplementation is being evaluated as potential therapy for hypertension and vascular dysfunction in ASL deficiency [NCT02252770, NCT03064048, Nagamani et al 2012b]. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Argininosuccinate Lyase Deficiency

c0268547

gene_reviews

https://www.ncbi.nlm.nih.gov/books/NBK51784/

{"mesh": ["D056807"], "synonyms": ["Argininosuccinic Acid Lyase Deficiency", "Argininosuccinic Aciduria", "ASLD"]}

Iridodialysis Other namesCoredialysis Iridodialysis caused by blunt trauma to the eye SpecialtyOphthalmology Iridodialysis, is a localized separation or tearing away of the iris from its attachment to the ciliary body.[1][2] ## Contents * 1 Symptoms and signs * 1.1 Complications * 2 Causes * 3 Treatment * 4 See also * 5 References * 6 External links ## Symptoms and signs[edit] Those with small iridodialyses may be asymptomatic and require no treatment, but those with larger dialyses may have corectopia or polycoria and experience monocular diplopia, glare, or photophobia.[3][4][5] Iridodialyses often accompany angle recession[6] and may cause glaucoma[7] or hyphema.[8] Hypotony may also occur.[9] ### Complications[edit] Those with traumatic iridodialyses (particularly by blunt trauma) are at high risk for angle recession, which may cause glaucoma.[3] This is typically seen about 100 days after the injury, and as such is sometimes called "100-day glaucoma". Medical or surgical treatment to control the IOP may be required if glaucoma is present.[7] Soft, opaque contact lenses may be used to improve cosmesis and reduce the perception of double vision.[7][3] ## Causes[edit] Iridodialyses are usually caused by blunt trauma to the eye,[2] but may also be caused by penetrating eye injuries.[7] An iridodialysis may be an iatrogenic complication of any intraocular surgery[10][11][12] and at one time they were created intentionally as part of intracapsular cataract extraction.[13] Iridodialyses have been reported to have occurred from boxing,[14] airbag deployments,[15] high-pressure water jets,[16] elastic bungee cords,[17][18] bottle caps opened under pressure,[19] water balloons,[20] fireworks,[21][22] and various types of balls.[23] ## Treatment[edit] Iridodialysis causing an associated hyphema has to be carefully managed, and recurrent bleeds should be prevented by strict avoidance of all sporting activities. Management typically involves observation and bed rest. Red blood cells may decrease the outflow of aqueous humor, therefore the eye pressure should be kept low by giving oral acetazolamide (a diuretic given to reduce intraoccular pressure). Accidental trauma during sleep should be prevented by patching with an eye shield during night time. Avoid giving aspirin, heparin/warfarin and observe daily for resolution or progression. A large hyphema may require careful anterior chamber washout. Rebleeds may require additional intervention and therapy. Later, surgical repair may be considered for larger avulsions causing significant double vision, cosmesis or glare symptoms.[4] Surgical repair is usually done by 10-0 prolene suture taking the base of iris avulsion and suturing it to the scleral spur and ciliary body junction. ## See also[edit] * Eye injury ## References[edit] 1. ^ Cline D; Hofstetter HW; Griffin JR. Dictionary of Visual Science. 4th ed. Butterworth-Heinemann, Boston 1997. ISBN 0-7506-9895-0 2. ^ a b Cassin, B. and Solomon, S. Dictionary of Eye Terminology. Gainesville, Florida: Triad Publishing Company, 1990. 3. ^ a b c Rappon JM. "Ocular Trauma Management for the Primary Care Provider." Pacific University College of Optometry. Accessed October 12, 2006. Archived September 1, 2006, at the Wayback Machine 4. ^ a b "Cornea & External Diseases: Trauma: Traumatic Iridodialysis." Archived 2017-10-18 at the Wayback Machine Digital Reference of Ophthalmology. Accessed October 11, 2006. 5. ^ Brown, SM (1998). "A technique for repair of iridodialysis in children". Journal of AAPOS. 2 (6): 380–2. doi:10.1016/S1091-8531(98)90041-6. PMID 10532731. 6. ^ Sullivan BR. "Glaucoma, Angle Recession". eMedicine.com. August 16, 2006. Accessed October 11, 2006. 7. ^ a b c d "Glaucoma: Angle Closure: Traumatic Iridodialysis." Archived 2017-05-31 at the Wayback Machine Digital Reference of Ophthalmology. Accessed October 11, 2006. 8. ^ Kiel, J; Chen, S (2001). "Contusion injuries and their ocular effects" (PDF). Clinical & Experimental Optometry. 84 (1): 19–25. doi:10.1111/j.1444-0938.2001.tb04931.x. PMID 12366340. Archived from the original (PDF) on 2006-09-27. Retrieved 2006-10-11. 9. ^ Behndig, A. (2002). "Results with a modified method for scleral suturing of intraocular lenses". Acta Ophthalmologica Scandinavica. 80 (1): 16–18. doi:10.1034/j.1600-0420.2002.800104.x. PMID 11906298. 10. ^ "Manual Small Incision Cataract Surgery: Intraoperative Complications." Archived 2012-02-05 at the Wayback Machine ORBIS International Inc. Accessed October 11, 2006. 11. ^ Gashau, AG; Anand, A; Chawdhary, S (2006). "Hydrophilic acrylic intraocular lens exchange: Five-year experience". Journal of Cataract and Refractive Surgery. 32 (8): 1340–4. doi:10.1016/j.jcrs.2006.02.062. PMID 16863972. 12. ^ Walker, NJ; Foster, A; Apel, AJ (2004). "Traumatic expulsive iridodialysis after small-incision sutureless cataract surgery". Journal of Cataract and Refractive Surgery. 30 (10): 2223–4. doi:10.1016/j.jcrs.2004.03.040. PMID 15474840. 13. ^ Beetham, WP. (1941). "Cataract Extraction with Iridodialysis". Trans. Am. Ophthalmol. Soc. 39: 104–15. PMC 1315004. PMID 16693243. 14. ^ Hazar, M; Beyleroglu, M; Subasi, M; Or, M (2002). "Ophthalmological findings in elite amateur Turkish boxers". British Journal of Sports Medicine. 36 (6): 428–30. doi:10.1136/bjsm.36.6.428. PMC 1724577. PMID 12453836. 15. ^ Kenney, KS; Fanciullo, LM (2005). "Automobile air bags: friend or foe? A case of air bag-associated ocular trauma and a related literature review". Optometry. 76 (7): 382–6. doi:10.1016/j.optm.2005.06.001. PMID 16038865. 16. ^ Gracner, B; Pahor, D (2001). "Bilateral eye injury caused by a high-pressure water jet from a fire hose". Wiener Klinische Wochenschrift. 113 Suppl 3: 62–4. PMID 15503624. 17. ^ Viestenz, A; Küchle, M (2002). "Ocular contusion caused by elastic cords: a retrospective analysis using the Erlangen Ocular Contusion Registry". Clinical & Experimental Ophthalmology. 30 (4): 266–9. doi:10.1046/j.1442-9071.2002.00529.x. PMID 12121366. 18. ^ Chorich Lj, 3rd; Davidorf, FH; Chambers, RB; Weber, PA (1998). "Bungee cord-associated ocular injuries". American Journal of Ophthalmology. 125 (2): 270–2. doi:10.1016/S0002-9394(99)80111-1. PMID 9467466. 19. ^ Viestenz, A; Küchle, M (2002). "Eye contusions caused by a bottle cap. A retrospective study based on the Erlangen Ocular Contusion Register (EOCR)". Der Ophthalmologe. 99 (2): 105–8. doi:10.1007/s003470100504. PMID 11871070. 20. ^ Bullock, JD; Ballal, DR; Johnson, DA; Bullock, RJ (1997). "Ocular and orbital trauma from water balloon slingshots. A clinical, epidemiologic, and experimental study". Ophthalmology. 104 (5): 878–87. doi:10.1016/s0161-6420(97)30218-8. PMID 9160038. 21. ^ Arya, SK; Malhotra, S; Dhir, SP; Sood, S (September 2001). "Ocular fireworks injuries. clinical features and visual outcome". Indian Journal of Ophthalmology. 49 (3): 189–90. PMID 15887729. 22. ^ Sacu, S; Ségur-Eltz, N; Stenng, K; Zehetmayer, M (2002). "Ocular firework injuries at New Year's eve". Ophthalmologica. 216 (1): 55–9. doi:10.1159/000048298. PMID 11901290. 23. ^ Purdie, AT; Whyte, IF (1998). "Shinty and ocular trauma in north west Scotland". British Journal of Ophthalmology. 82 (12): 1445. doi:10.1136/bjo.82.12.1444a. PMC 1722457. PMID 9930282. ## External links[edit] Classification D * ICD-10: H21.5 * ICD-10-CM: H21.53 * ICD-9-CM: 364.76 * SNOMED CT: 45953007 * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Iridodialysis

c0152246

wikipedia

https://en.wikipedia.org/wiki/Iridodialysis

{"umls": ["C0152246"], "icd-9": ["364.76"], "icd-10": ["H21.5"], "wikidata": ["Q5927780"]}

A number sign (#) is used with this entry because Hurler-Scheie syndrome is caused by homozygous or compound heterozygous mutation in the gene encoding alpha-L-iduronidase (IDUA; 252800) on chromosome 4p16. Description The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH; 607014), Scheie (MPS IS; 607016), and Hurler-Scheie (MPS IH/S) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972). Roubicek et al. (1985) presented 5 patients with alpha-L-iduronidase deficiency and a phenotype atypical for both Hurler and Scheie syndromes. They felt that the genetic compound explanation was acceptable for some cases, but that others must represent different mutations. Clinical Features The clinical features of Hurler-Scheie syndrome include short stature, corneal clouding, joint stiffening, umbilical hernia, dysostosis multiplex, hepatosplenomegaly, and little to no intellectual dysfunction. Onset of symptoms occurs between ages 3 and 8 years. Survival to adulthood is typical (Neufeld and Muenzer, 2001). ### Head and Neck The facial features somewhat resemble those of Hurler syndrome. The nasal bridge is depressed and there is micrognathia. The mouth is usually broad. Corneal clouding and abnormal electroretinogram are characteristic findings (Whitley, 1993). ### Cardiovascular Features Gross et al. (1988) studied 4 Hurler-Scheie patients clinically and echocardiographically. Their ages ranged from 5 to 11 years. Of the 4 patients, 3 had insignificant auscultatory findings and 1 had evidence of moderate mitral regurgitation with a diastolic flow rumble. Echocardiogram revealed thickening of the mitral valve leaflets and a dilated left atrium and left ventricle. The others all had thickening of the mitral valve leaflets and a dilated left atrium and left ventricle. The others all had thickened mitral valves. One patient with increasing upper airway obstruction had discrete bulging of the interventricular septum into the left ventricular outflow tract. Cardiac catheterization revealed mild pulmonary hypertension and tracheostomy was performed. ### Respiratory Features Frequent respiratory infections, limited chest expansion, and difficulties with endotracheal intubation are all features of MPS IH/S (Whitley, 1993). Tracheal stenosis was reported in a 23-year-old woman with MPS IH/S who died during attempted endotracheal intubation (Wassman et al., 1982). Semenza and Pyeritz (1988) studied respiratory complications in 3 patients with MPS IH/S. All had tongue enlargement and nasopharyngeal obstruction. Tonsillar hypertrophy was found in two-thirds of the patients. One patient studied by polysomnography was found to have obstructive sleep apnea. Shapiro et al. (1985) described a patient with MPS IH/S with severe scoliosis and a history of marked snoring and restless sleep. Tonsillectomy and adenoidectomy provided little change in symptomatology. Polysomnogram revealed obstructive sleep apnea with oxygen saturation ranging from 61 to 87%. ### Musculoskeletal System The radiographic features of Hurler-Scheie syndrome are intermediate in the spectrum of dysostosis multiplex. Schmidt et al. (1987) described the radiologic changes in 2 patients with MPS type I H/S. Radiologic findings revealed enlargement of the sella in 1 patient and basilar skull impression in the other. Sclerosis and thickening of the base of the skull was observed in both patients. They showed irregularities of the acromial joints and acetabula, hypoplasia of the inferior portion of the iliac bones, and flared iliac wings. The flat femurs had short metaphyses and were held in valgus position. The skeletal changes of the spine and hands were minimal. Joint stiffness is a common feature of all the MPS disorders with the exception of Morquio syndrome (253000; 253010). The joint function abnormalities probably result from a combination of the metaphyseal deformities and thickened joint capsules secondary to glycosaminoglycan deposition and fibrosis (Neufeld and Muenzer, 2001). Progressive lumbar gibbus or kyphosis is commonly seen in the MPS disorders (Neufeld and Muenzer, 2001). Semenza and Pyeritz (1988) described 3 patients with MPS IH/S. Two patients had thoracic hyperkyphosis and scoliosis. Two patients were studied for cervical spine involvement such as odontoid hypoplasia or c1-2 subluxation. Neither had evidence of abnormality. ### Nervous System Mental function is often preserved, but some patients have intellectual decline with age (Whitley, 1993). Pachymeningitis cervicalis (compression of the cervical cord secondary to glycosaminoglycan in the dura) occurs in MPS IH/S. However, communicating hydrocephalus appears to be uncommon. Spondylolisthesis of the lower spine can lead to spinal cord compression and myelopathy (Neufeld and Muenzer, 2001). Winters et al. (1976) described a case of alpha-L-iduronidase deficiency that differed from the Hurler and Scheie syndromes and may represent the Hurler-Scheie compound. The female patient died at age 25 years. She was 10 years old before she was noted to be academically slow. She could not perform normally in physical education. Although she was graduated from high school at age 20, she never received a grade higher than D in high school. In the last 5 years of life remarkable coarsening of her facial features occurred. She presented to medical attention because of acute paranoia. Autopsy findings were described. Psychosis was also described by Dugas et al. (1985) in a 17.5-year-old patient with MPS IH/S. ### Other Features Schiro et al. (1996) described grouped papules on the extensor surface of the upper portions of the arms and legs as an initial presenting feature in a 5-year-old boy with Hurler-Scheie syndrome. Other physical findings included progressive flexion contractures and mild developmental delay. Biochemical Features The IDUA enzyme deficiency in Hurler-Scheie compound fibroblasts is intermediate between that in Hurler and Scheie syndromes (Fujibayashi et al., 1984). Schuchman and Desnick (1988) reported the presence of cross-reactive immunologic material (CRIM) in individuals from each of the 3 MPS I subtypes. Furthermore, they identified effector compounds that enhanced the residual activities in subtype extracts into the heterozygote range. The polyclonal antibody with which this work was done, however, is under suspicion because of the findings of Scott et al. (1990) that it gave a fallacious result when used for the mapping of the IDUA gene in somatic cell hybrids. Inheritance Jensen et al. (1978) observed brother and sister, children of first-cousin Pakistani parents, with the Hurler-Scheie phenotype, including receding chin. The parental consanguinity suggested that their alpha-L-iduronidase deficiency was due to homozygosity for an allele at that locus, not compound heterozygosity. The same is true in the 2 families with first-cousin parents reported by Kaibara et al. (1979), in each of which 2 sibs had the Hurler-Scheie phenotype. Bunge et al. (1995) confirmed that Hurler-Scheie syndrome is an autosomal recessive disorder. Clinical Management Wang et al. (2009) reported 2 brothers with intermediate MPS I diagnosed at ages 4 years and 3 months, respectively. Both were cognitively normal, even though both had white matter abnormalities and ventricular dilatation on brain MRI, which were more severe in the older brother. Treatment with intravenous enzyme replacement therapy (ERT) resulted in progressive improvement in brain MRI findings in both patients. The findings suggested that ERT may improve brain MRI abnormalities in patients with MPS, even though ERT had previously been thought not to cross into the brain. Wang et al. (2009) offered some explanations, including lessening of somatic GAG accumulation, repair of damaged brain endothelium, and possibly small amounts of enzyme being able to permeate the brain. Wang et al. (2011) described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. Molecular Genetics Bunge et al. (1995) identified 13 novel and 7 previously reported mutations of the IDUA gene, covering 88% of mutant alleles and 86% of genotypes, in a total of 29 patients with MPS I of differing clinical severity. Lee-Chen and Wang (1997) identified a homozygous T364M mutation (252800.0018) of the IDUA gene in a 10-year-old Chinese patient with Hurler-Scheie syndrome. Lee-Chen et al. (1999) identified the molecular lesion in an 18-year-old patient with intermediate phenotype classified as the Hurler-Scheie syndrome: short stature, mild coarse face, corneal clouding, and skeletal deformities with atlantoaxial dislocation. The patient showed normal intelligence based on excellent performance in school. As a result of loss of mobility, she was wheelchair-bound and educated at home. She was found to be homozygous for an R619G mutation (252800.0017). In a mutation analysis of 85 mucopolysaccharidosis type I families, Beesley et al. (2001) identified 165 of the 170 mutant alleles. Despite the high frequency of W402X (252800.0001) and Q70X (252800.0002), the identification of many novel mutations unique to individual families further highlighted the genetic heterogeneity of MPS I. Population Genetics Yamagishi et al. (1996) defined the IDUA mutations in 19 Japanese MPS I patients, including 2 pairs of sibs, with various clinical phenotypes; Hurler syndrome, 6 cases; Hurler/Scheie syndrome, 7 cases; Scheie syndrome, 6 cases. Two common mutations accounted for 42% of the 38 alleles in these patients. One was a novel 5-bp insertion between the T at nt704 and the C at nucleotide 705 (704ins5; 252800.0014), which was seen only in the Japanese population. The other was a missense mutation, R89Q (252800.0015), which is seen also in Caucasians, although uncommonly. No Japanese patient was found to carry the W402X (252800.0001) or Q70X (252800.0002) alleles, the 2 most common MPS I mutations in Caucasians. Homozygosity for the 704ins5 mutation was associated with a severe phenotype; homozygosity for the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for these 2 mutations produced an intermediate phenotype. Haplotype analysis using polymorphisms linked to IDUA locus demonstrated that each of these 2 common mutations occurred on a different specific haplotype, suggesting that individuals with each of these common mutations derived from a common founder. The mild-intermediate-severe phenotypic relationships of the 2 common Japanese mutations fulfill the prediction of McKusick et al. (1972). INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Micrognathia Eyes \- Corneal clouding Nose \- Low nasal bridge Mouth \- Prominent lips CARDIOVASCULAR Heart \- Mitral valve regurgitation \- Thickening of the mitral valve leaflets \- Aortic valve thickening \- Aortic valve regurgitation \- Dilated left atrium \- Dilated left ventricle Vascular \- Pulmonary hypertension, mild RESPIRATORY \- Obstructive sleep apnea \- Recurrent respiratory infections Nasopharynx \- Nasopharyngeal obstruction \- Hypertrophic tonsils Airways \- Tracheal stenosis ABDOMEN External Features \- Umbilical hernia Liver \- Hepatomegaly Spleen \- Splenomegaly SKELETAL \- Dysostosis multiplex \- Joint stiffness Spine \- Scoliosis \- Kyphosis \- Progressive lumbar gibbus Limbs \- Flat femurs with short metaphyses SKIN, NAILS, & HAIR Skin \- Thick skin Hair \- Hirsutism NEUROLOGIC Central Nervous System \- Pachymeningitis cervicalis (cervical cord compression due to thickened dura) LABORATORY ABNORMALITIES \- Excretion of heparan sulfate in urine \- Excretion of dermatan sulfate in urine MISCELLANEOUS \- Onset of symptoms between ages 3-8 years of age \- Treatment with enzyme replacement therapy \- Alpha-L-iduronidase activity is <1% for all forms of MPS1 \- MPS1 types are distinguished clinically by age of onset and progression or by mutation(s) MOLECULAR BASIS \- Caused by mutation in the alpha-L-iduronidase gene (IDUA, 252800.0012 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

HURLER-SCHEIE SYNDROME

c0086431

omim

https://www.omim.org/entry/607015

{"doid": ["12802"], "mesh": ["D008059"], "omim": ["607015"], "icd-10": ["E76.02"], "orphanet": ["93476", "579"], "synonyms": ["Alternative titles", "MUCOPOLYSACCHARIDOSIS TYPE IH/S"], "genereviews": ["NBK1162"]}

A number sign (#) is used with this entry because of evidence that combined cerebellar and peripheral ataxia with hearing loss and diabetes mellitus (ACPHD) is caused by homozygous mutation in the DNAJC3 gene (601184) on chromosome 13q32. One such family has been reported. Clinical Features Synofzik et al. (2014) reported 3 adult sibs, from a 'likely consanguineous' (Synofzik, 2015) Turkish family, with juvenile-onset insulin-dependent diabetes mellitus and central and peripheral nervous system abnormalities. The neurologic features included combined cerebellar and afferent ataxia, mild upper motor neuron damage, demyelinating sensorimotor peripheral neuropathy, and sensorineural hearing loss. All 3 patients had onset of diabetes between 15 and 18 years of age. The age at onset of the neurologic features ranged widely: 1 sib had onset of hearing loss and gait disturbances at age 6, another had onset of these symptoms in the teenage years, and the third had onset of hearing loss at age 27 and gait disturbances at age 34. The patients also had an 'isolated cognitive deficit in backward calculation of serial sevens.' Synofzik et al. (2014) also reported 2 sisters, born of consanguineous parents, with a similar disorder. The sisters were 20 and 14 years old and had onset of insulin-dependent diabetes mellitus at ages 14 and 11 years, respectively. One sister had onset of hearing loss and gait disturbance at age 2 years, whereas the other had normal hearing and onset of gait disturbance at age 11 years. All 5 patients had short stature and low body mass index, as well as biochemical evidence of residual endogenous insulin secretion. One patient from each family had extensor plantar responses, indicating upper motor neuron damage. Brain imaging of 1 patient from each family showed generalized supra- and infratentorial cerebral atrophy pronounced in the cervical cord, cerebellum, and midbrain. Inheritance The transmission pattern of ACPHD in the families reported by Synofzik et al. (2014) was consistent with autosomal recessive inheritance. Cytogenetics In 2 sisters, born of consanguineous parents, with ACPHD, Synofzik et al. (2014) identified a homozygous 72-kb deletion in the DNAJC3 gene, resulting in the deletion of exons 6 to 12 of DNAJC3 and the last exon of the neighboring UGGT2 gene (605898), which is transcribed in the opposite direction. The proband in this family was ascertained from 8 individuals with a similar phenotype who underwent Sanger sequencing of the DNAJC3 gene. Patient fibroblasts showed absence of the DNAJC3 protein. Synofzik (2015) stated that this family was Turkish. Molecular Genetics In 3 sibs from a Turkish family with ACPHD, Synofzik et al. (2014) identified a homozygous truncating mutation in the DNAJC3 gene (R194X; 601184.0001). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Patient fibroblasts showed absence of the DNAJC3 protein. There were no morphologic or functional abnormalities of the endoplasmic reticulum (ER) in patient fibroblasts, but Synofzik et al. (2014) noted that such changes may be found only in specific tissues, such as pancreas or neurons, which were not available for testing. (There was a discrepancy in the article by Synofzik et al. (2014) regarding consanguinity in this family; Synofzik (2015) stated that the family was 'likely consanguineous.') Animal Model Ladiges et al. (2005) found that Dnajc3-null mice developed glucosuria and hyperglycemia associated with decreased insulin resulting from increased apoptosis of pancreatic islet cells. Mutant mice were also smaller than control mice due to decreased body fat. Ladiges et al. (2005) noted that Dnajc3 acts to downregulate the ER stress response, and suggested that their findings implicated a role for ER stress-mediated apoptosis in the development of diabetes mellitus. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Low body mass index HEAD & NECK Ears \- Sensorineural hearing loss NEUROLOGIC Central Nervous System \- Gait ataxia \- Extensor plantar responses (in some patients) \- Cognitive deficits, mild (in some patients) \- Cerebral atrophy \- Cerebellar atrophy \- Brainstem atrophy \- Spinal cord atrophy Peripheral Nervous System \- Demyelinating sensorimotor peripheral neuropathy \- Areflexia of the lower limbs Decreased nerve conduction velocities ENDOCRINE FEATURES \- Insulin-dependent diabetes mellitus MISCELLANEOUS \- Onset of diabetes in teenage years \- Onset of neurologic features is variable, even within the same family (range early childhood to adult) \- One likely consanguineous Turkish family has been reported (last curated January 2015) MOLECULAR BASIS \- Caused by mutation in the DNAJ/HSP40 homolog, subfamily C, member 3 gene (DNAJC3, 601184.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

ATAXIA, COMBINED CEREBELLAR AND PERIPHERAL, WITH HEARING LOSS AND DIABETES MELLITUS

c4015436

omim

https://www.omim.org/entry/616192

{"omim": ["616192"], "orphanet": ["445062"], "synonyms": ["Combined cerebellar and peripheral ataxia-hearing loss-diabetes mellitus syndrome"]}

Spastic ataxia-corneal dystrophy syndrome is a rare, hereditary ataxia disorder characterized by the presence of spastic ataxia in association with bilateral congenital cataract, macular corneal dystrophy (stromal with deposition of mucoid material) and nonaxial myopia. Patients present normal intellectual development. There have been no further descriptions in the literature since 1986. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Spastic ataxia-corneal dystrophy syndrome

c1849085

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2572

{"gard": ["3795"], "mesh": ["C536989"], "omim": ["271320"], "umls": ["C1849085"], "icd-10": ["G11.8"], "synonyms": ["Bedouin spastic ataxia syndrome", "Mousa-Al Din-Al Nassar syndrome", "Spastic ataxia-ocular anomalies syndrome"]}

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 15q14. The deleted region includes the MEIS2 gene (601740). Clinical Features Erdogan et al. (2007) reported a 4-year-old girl who presented at birth with cleft palate, atrial septal defect, and hypotonia. She subsequently showed delayed psychomotor development and moderate mental retardation. Mild dysmorphic features included low-set posteriorly rotated ears, short philtrum, and pointed chin. Array CGH identified a de novo heterozygous 5.3-Mb interstitial deletion of chromosome 15q14 that included the MEIS2 gene (601740). Johansson et al. (2014) reported 5 children, including 2 sibs, with heterozygous deletions involving chromosome 15q14. Two sisters shared a 0.6-Mb deletion that was maternally inherited, whereas the deletions in the other 3 patients occurred de novo; the latter 3 deletions ranged in size from 1.0 to 4.8 Mb. All patients had delayed motor development, and all but 1 had delayed intellectual development that was generally mild. The 2 sisters and 1 additional child had cleft palate; 1 of the sisters and 2 additional patients had ventricular septal defects. Only the patient with the 4.8-Mb deletion had clearly dysmorphic features, including lower-set ears, bulbous nose with wide and low columella, and everted upper lip. The other patients shared a high forehead, finely arched eyebrows, and mildly shortened philtrum with tented upper lip. The deleted region in all cases included the MEIS2 gene. Johansson et al. (2014) also reported a mother and her 3 children who had a heterozygous 58-kb duplication within the MEIS2 gene that was predicted to result in a frameshift and premature termination. All 4 family members had cleft palate, mildly delayed motor development, and mild intellectual disability (see 601740.0001). The findings in all 9 patients suggested that cleft palate is associated with haploinsufficiency for the MEIS2 gene. Conte et al. (2016) performed a bioinformatics and statistical analysis of copy number variations (CNV) associated with cleft lip/palate by examining 2 large CNV databases. After filtration, 5 of 312 patients were found to carry deletions involving the MEIS2 gene, suggesting that MEIS2 is a candidate gene for orofacial clefting. However, a large number of individuals (approximately 140) from a control database were also found to carry deletions involving the MEIS2 gene, and these deletions tended to disrupt the promoter region. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- High forehead \- Short philtrum Ears \- Low-set ears \- Posteriorly rotated ears Eyes \- Arched eyebrows Mouth \- Cleft palate \- Cleft lip \- Everted lower lip \- Tented upper lip CARDIOVASCULAR Heart \- Atrial septal defect \- Ventricular septal defect NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability, variable Behavioral Psychiatric Manifestations \- Autistic features (in some patients) MISCELLANEOUS \- Onset at birth \- Contiguous gene deletion syndrome MOLECULAR BASIS \- Contiguous gene deletion of between 0.6 - 4.8 Mb on chromosome 15q14 ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

CHROMOSOME 15q14 DELETION SYNDROME

c4225666

omim

https://www.omim.org/entry/616898

{"omim": ["616898"], "orphanet": ["261190"], "synonyms": ["Del(15)(q14)", "Monosomy 15q14"]}

Braxy is an infectious disease which causes sudden death in sheep. It is caused by the bacterium Clostridium septicum. Braxy generally occurs in winter, when sheep eat frosted root crops,[1] or frosted grass.[2] The frozen feed damages the mucosa (lining) of the abomasum, allowing C. septicum to enter, causing abomasitis and a fatal bacteremia.[3] Young sheep not protected with a vaccine are most commonly affected. If sheep are not found dead, signs include abdominal pain and recumbency.[2] There is no treatment,[1] and sheep usually die within 36 hours of the onset of signs.[4] The carcass of sheep which died of braxy will often decompose more rapidly than expected.[1] Historically, the mutton of affected sheep was also referred to as braxy.[5] A vaccine against braxy was developed at the Moredun Research Institute in Scotland.[6] Braxy has been reported in Europe (particularly in Iceland, Norway and the UK), Australia and the United States.[7] ## References[edit] 1. ^ a b c Scott, PR (2015). "Digestive system: Braxy". Sheep medicine (2nd ed.). CRC Press. p. 137. ISBN 9781498700153. 2. ^ a b Winter, AC (2012). "Chapter 10: Sudden death: Main clostridial diseases". A handbook for the sheep clinician (7th ed.). Wallingford: CABI. pp. 92–93. ISBN 9781845939939. 3. ^ Songer, JG (2010). "Chapter 12: Histotoxic Clostridia". In Gyles, CL; Prescott, JF; Songer, JG; Thoen, CO (eds.). Pathogenesis of bacterial infections in animals (4th ed.). Ames, Iowa: Wiley-Blackwell. pp. 203–209. ISBN 978-0-8138-1237-3. 4. ^ Prescott, JF; Menzies, PI; Fraser, RS (2016). "Chapter 17: Clostridial abomasitis". In Uzal, FA; Songer, JG; Prescott, JF; Popoff, MR (eds.). Clostridial diseases of animals. John Wiley & Sons. pp. 205–220. ISBN 9781118728307. 5. ^ Wood, James, ed. (1907). "Braxy" . The Nuttall Encyclopædia. London and New York: Frederick Warne. 6. ^ "Phone call reveals link to Moredun's past". Moredun Magazine (6): 1. 2013. Archived from the original on 2016-08-21. Retrieved 2016-08-04. 7. ^ Songer, JG (1998). "Clostridial diseases of small ruminants". Veterinary Research. 29 (3–4): 219–32. PMID 9689739. This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Braxy

c0275618

wikipedia

https://en.wikipedia.org/wiki/Braxy

{"wikidata": ["Q1781300"]}

An exceedingly rare, autosomal recessive immune disease characterized by thumb aplasia, short stature with skeletal abnormalities, and combined immunodeficiency described in three sibships from two possibly related families. The skeletal abnormalities included unfused olecranon and the immunodeficiency manifested with severe chickenpox and chronic candidiasis. No new cases have been reported since 1978. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Absent thumb-short stature-immunodeficiency syndrome

c1848818

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2951

{"mesh": ["C564770"], "omim": ["274190"], "umls": ["C1848818"], "icd-10": ["D82.8"]}

## Description Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700. Mapping Naiglin et al. (2002) performed linkage analysis in 21 French and 2 Algerian families with autosomal dominant high-grade myopia (refractive error greater than or equal to -6.00 diopters). They excluded previously identified myopia loci and found suggestive evidence of linkage to chromosome 7q36, with a maximum multipoint lod score of 2.81. No locus heterogeneity was detected. Paget et al. (2008) studied 26 families segregating high-grade myopia, including the families reported by Naiglin et al. (2002) and a subset of 9 newly collected families. A genomewide scan of the 9 new families showed no linkage to 7q36. Study of all 26 families with a parametric model did not yield a significant lod score (greater than 3), even for 7q36. However, a nonparametric model demonstrated significant linkage to chromosome 7p15 in all of the families (Z-NPL = 4.07, p = 0.00002). The interval was 7.81 cM between markers D7S2458 and D7S2515. Ciner et al. (2008) performed quantitative trait locus linkage analysis in African American families to identify genomic regions responsible for ocular refraction. They genotyped for 387 microsatellite markers in 398 individuals with a mean refraction of -2.87 diopters and at least 1 diopter in 267. Linkage was identified on chromosome 7p15 (maximum lod of 5.87) in a 17-Mb region between markers D7S1808 and D7S817. The authors noted that a previous study in European-derived families by Klein et al. (2007) had found evidence of linkage to chromosome 7p21. History Because Paget et al. (2008) found no evidence of linkage of myopia to chromosome 7q36, as had been reported by Naiglin et al. (2002), but instead found significant linkage to 7p15, the symbol MYP4 was originally used for the locus on 7p15. The study by Paget et al. (2008) included the families reported by Naiglin et al. (2002). INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Myopia, high-grade bilateral (range -5.50 to -50 diopters, average adult refractive error -13.925 diopters) \- Increased ocular axial length (35 mm vs. 24 mm in normal non-myopes) \- Multiple retinal holes \- Presenile cataract ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MYOPIA 17, AUTOSOMAL DOMINANT

c3888211

omim

https://www.omim.org/entry/608367

{"omim": ["608367"], "synonyms": ["Alternative titles", "MYOPIA 4, FORMERLY"]}

A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-8 (MCPH8) is caused by homozygous mutation in the CEP135 gene (611423) on chromosome 4q. For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). Clinical Features Hussain et al. (2012) reported 2 sibs, born of consanguineous Pakistani parents, with primary microcephaly apparent at birth. Each had a sloping forehead, retrognathia, severe cognitive deficits, and unintelligible speech at age 5 years. One died at age 11 years. The head circumferences ranged between -12 and -14.5 SD. No other abnormalities were noted. Farooq et al. (2016) reported 2 sibs, born of consanguineous Pakistani parents, with MCPH8. The patients had severe learning disabilities and speech impairment, but no seizures. Their head circumferences at the age of 10 and 7 years were -14 and -12 SD, respectively. Inheritance The transmission pattern of primary microcephaly in the family reported by Hussain et al. (2012) was consistent with autosomal recessive inheritance. Molecular Genetics In 2 sibs, born of consanguineous Pakistani parents, with autosomal recessive primary microcephaly-8, Hussain et al. (2012) identified a homozygous truncating mutation in the CEP135 gene (611423.0001). The mutation was identified by genomewide linkage analysis followed by candidate gene sequencing, and was not found in 384 Pakistani controls. Whole-exome sequencing of 1 of the patients did not identify other potentially pathogenic mutations that could be responsible for the disorder. The parents were healthy with normal head circumference; the father carried the mutation in heterozygous state. Cultured patient fibroblasts showed poor growth and had increased numbers of fragmented centrosomes per cell compared to controls. The microtubule network was frequently disorganized (55% of the cells) and showed cell shape changes as well as misshapen and fragmented nuclei. Approximately 22% of mutant patient fibroblasts were without centrosomes, which was never observed in control cells. In vitro functional expression studies of the mutant protein in COS-7 cells caused abnormal disorganized microtubule networks, and the mutant protein did not localize to the centrosome. The findings indicated that CEP135 is an essential component of the centrosome. In 2 sibs, born of consanguineous Pakistani parents, with MCPH8, Farooq et al. (2016) identified a homozygous splice site mutation in the CEP135 gene (611423.0002). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was predicted to result in nonsense-mediated mRNA decay, but if translated, the mutant protein would lack the C-terminal hSAS-6 interacting domain and would most likely result in multiple and fragmented centrosomes with disorganized microtubules. INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (-12 to -14.5 SD) \- Sloping forehead Face \- Retrognathia NEUROLOGIC Central Nervous System \- Mental retardation, severe \- Unintelligible speech MISCELLANEOUS \- Onset at birth \- Two unrelated consanguineous Pakistani families have been reported (last curated March 2017) MOLECULAR BASIS \- Caused by mutation in the 135-kD centrosomal protein gene (CEP135, 611423.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MICROCEPHALY 8, PRIMARY, AUTOSOMAL RECESSIVE

c3711387

omim

https://www.omim.org/entry/614673

{"doid": ["0070282"], "mesh": ["C579935"], "omim": ["614673"], "orphanet": ["2512"]}

Spindle cell rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma first described by Cavazzana, Schmidt and Ninfo in 1992.[1] This subtype has a more favorable clinical course and prognosis than usual embryonal rhabdomyosarcoma. Spindle cell rhabdomyosarcoma typically occurs in young males and most commonly occurs in paratesticular soft tissue, followed by the head and neck. ## References[edit] 1. ^ Cavazzana, A. O.; D. Schmidt; V. Ninfo (1992). "Spindle cell rhabdomyosarcoma: a prognostically favorable variant of rhabdomyosarcoma". American Journal of Surgical Pathology. USA: Lippincott Williams & Wilkins. 16 (3): 229–235. doi:10.1097/00000478-199203000-00002. PMID 1599014. This article about a neoplasm is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Spindle cell rhabdomyosarcoma

c1266134

wikipedia

https://en.wikipedia.org/wiki/Spindle_cell_rhabdomyosarcoma

{"umls": ["C1266134"], "wikidata": ["Q7577499"]}

Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (endometrial cancer). Women with Lynch syndrome have a higher overall risk of developing cancer than men with the condition because of these cancers of the female reproductive system. Individuals with Lynch syndrome typically develop cancer in their forties or fifties. People with Lynch syndrome may occasionally have noncancerous (benign) growths in the colon, called colon polyps. In individuals with this disorder, colon polyps occur at a younger age but not in greater numbers than they do in the general population. ## Frequency In the United States, it is estimated that 1 in 279 individuals have a gene mutation associated with Lynch syndrome. ## Causes Changes in the MLH1, MSH2, MSH6, PMS2, or EPCAM gene have been found in people with Lynch syndrome. The MLH1, MSH2, MSH6, and PMS2 genes are involved in repairing errors that occur when DNA is copied in preparation for cell division (a process called DNA replication). Because these genes work together to fix DNA errors, they are known as mismatch repair (MMR) genes. Mutations in any of these genes prevent the proper repair of DNA replication errors. As the abnormal cells continue to divide, the accumulated errors can lead to uncontrolled cell growth and possibly cancer. Mutations in the MLH1 or MSH2 gene tend to lead to a higher risk (70 to 80 percent) of developing cancer in a person's lifetime, while mutations in the MSH6 or PMS2 gene have a lower risk (25 to 60 percent)of cancer development. Mutations in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process. The EPCAM gene lies next to the MSH2 gene on chromosome 2 and certain EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated). As a result, the MSH2 gene's role in DNA repair is impaired, which can lead to accumulated DNA errors and cancer development. Although mutations in these genes predispose individuals to cancer, not all people with these mutations develop cancerous tumors. ### Learn more about the genes associated with Lynch syndrome * EPCAM * MLH1 * MSH2 * MSH6 * PMS2 ## Inheritance Pattern Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene in each cell is sufficient to increase cancer risk. It is important to note that people with a mutation have an increased risk of cancer; not all people who inherit mutations in these genes will develop cancer. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Lynch syndrome

c1527249

medlineplus

https://medlineplus.gov/genetics/condition/lynch-syndrome/

{"gard": ["9905"], "mesh": ["D015179"], "omim": ["114500", "120435"], "synonyms": []}

Ischemic Cardiomyopathy Atherosclerosis one of the causes of this condition Pronunciation * /ɪˈskiːmɪk/ SpecialtyCardiology SymptomsSudden fatigue CausesAtherosclerosis, Vasospasm[1] Diagnostic methodMRI[2] TreatmentPercutaneous intervention[3] Ischemic cardiomyopathy is a type of cardiomyopathy caused by a narrowing of the coronary arteries which supply blood to the heart.[4] Typically, patients with ischemic cardiomyopathy have a history of acute myocardial infarction,[5] however, it may occur in patients with coronary artery disease, but without a past history of acute myocardial infarction. This cardiomyopathy is one of the leading causes of sudden cardiac death.[6] The adjective ischemic means characteristic of, or accompanied by, ischemia — local anemia due to mechanical obstruction of the blood supply.[citation needed] ## Contents * 1 Signs and symptoms * 2 Cause * 3 Pathophysiology * 4 Diagnosis * 5 Management * 5.1 Prognosis * 6 References * 7 Further reading * 8 External links ## Signs and symptoms[edit] Signs and symptoms of ischemic cardiomyopathy include sudden fatigue, shortness of breath, dizziness, and palpitations.[citation needed] ## Cause[edit] Ischemic cardiomyopathy is the cause of more than 60% of all cases of systolic congestive heart failure in most countries of the world.[6][7] A chest radiograph that demonstrates coronary artery calcification is a probable indication of ischemic cardiomyopathy.[8] The following are causes of ischemic cardiomyopathy:[1] * Diabetes * Atherosclerosis * Vasospasm * Inflammation of arteries ## Pathophysiology[edit] Ischemic cardiomyopathy is caused by too little blood flow and hence oxygen reaching the muscular layer of the heart due to a narrowing of coronary arteries in turn causing cell death. This can cause different levels of tissue injury and affect large and intermediate arteries alike.[9][10][11] ## Diagnosis[edit] Ischemic cardiomyopathy can be diagnosed via magnetic resonance imaging (MRI) protocol, imaging both global and regional function. Also the Look-Locker technique is used to identify diffuse fibrosis; it is therefore important to be able to determine the extent of the ischemic scar.[2] Some argue that only left main- or proximal-left anterior descending artery disease is relevant to the diagnostic criteria for ischemic cardiomyopathy.[5] Myocardial imaging usually demonstrates left ventricular dilation, severe ventricular dysfunction, and multiple infarctions.[12] Signs include congestive heart failure, angina edema, weight gain and fainting, among others.[6][13] ## Management[edit] Play media Cardiac-Stem-Cells Restoring adequate blood flow to the heart muscle in people with heart failure and significant coronary artery disease is strongly associated with improved survival, some research showing up to 75% survival rates over 5 years.[14][15] A stem cell study indicated that using autologous cardiac stem cells as a regenerative approach for the human heart (after a heart attack) has great potential.[16] American Heart Association practice guidelines recommend implantable cardioverter-defibrillator (ICD) use in those with ischemic cardiomyopathy (40 days post-MI) that are (NYHA) New York Heart Association functional class I. A LVEF measurement (simply called LVEF alone among cardiologists) of greater than (>) 30% is often used to differentiate primary from ischemic cardiomyopathy, and as a prognostic indicator.[17][18] Coronary artery bypass surgery A 2004 study showed the patients in that study who underwent ventricular restoration as well as a coronary artery bypass achieved greater postoperative LVEF than with the latter surgery alone.[19] Severe cases are treated with heart transplantation.[20] ### Prognosis[edit] One of the most important features differentiating ischemic cardiomyopathy from the other forms of cardiomyopathy is the shortened, or worsened all-cause mortality in patients with ischemic cardiomyopathy. According to several studies, coronary artery bypass graft surgery has a survival advantage over medical therapy (for ischemic cardiomyopathy) across varied follow-ups.[10][21][22][23] ## References[edit] 1. ^ a b Bisognano, John D.; Baker, Marc L.; Earley, Mary Beth (2009-04-09). Manual of Heart Failure Management. Springer Science & Business Media. p. 50. ISBN 9781848821859. 2. ^ a b Hodler, Jurg (2015). Diseases of the Chest and Heart: Diagnostic Imaging and Interventional. Springer. p. 146. ISBN 978-88-470-5751-7. Retrieved 10 September 2015. 3. ^ Burke, Allen P.; Tavora, Fabio (2010). Practical Cardiovascular Pathology. Lippincott Williams & Wilkins. p. 96. ISBN 9781605478418. Retrieved 2 January 2018. 4. ^ "Cardiomyopathy: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-09-09. 5. ^ a b Felker, G.Michael; Shaw, Linda K; O’Connor, Christopher M (January 2002). "A standardized definition of ischemic cardiomyopathy for use in clinical research". Journal of the American College of Cardiology. 39 (2): 210–218. doi:10.1016/S0735-1097(01)01738-7. PMID 11788209. 6. ^ a b c Reynolds Delgado (21 April 2009). Interventional Treatment of Advanced Ischemic Heart Disease. Springer Science & Business Media. pp. 39–. ISBN 978-1-84800-395-8. 7. ^ Griffin, Brian P. (2012-10-01). Manual of Cardiovascular Medicine. Lippincott Williams & Wilkins. p. 130. ISBN 9781451131604. 8. ^ Brant, William E.; Helms, Clyde A. (2007-01-01). Fundamentals of Diagnostic Radiology. Lippincott Williams & Wilkins. p. 635. ISBN 9780781761352. 9. ^ Anversa, Piero; Sonnenblick, Edmund H. (1990). "Ischemic cardiomyopathy: Pathophysiologic mechanisms". Progress in Cardiovascular Diseases. 33 (1): 49–70. doi:10.1016/0033-0620(90)90039-5. ISSN 0033-0620. PMID 2142312. 10. ^ a b Yatteau, Ronald F.; Peter, Robert H.; Behar, Victor S.; Bartel, Alan G.; Rosati, Robert A.; Kong, Yihong (1974). "Ischemic cardiomyopathy: The myopathy of coronary artery disease". The American Journal of Cardiology. 34 (5): 520–525. doi:10.1016/0002-9149(74)90121-0. ISSN 0002-9149. PMID 4278154. 11. ^ Mann DL, Zipes DP, Libby P, Bonow RO (30 July 2014). Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Elsevier Health Sciences. pp. 1225–. ISBN 978-0-323-29064-7. 12. ^ E. van der Wall; K.J. Lie (6 December 2012). Recent Views on Hypertrophic Cardiomyopathy. Springer Science & Business Media. pp. 43–. ISBN 978-94-009-4994-2. 13. ^ Allen P. Burke; Fabio Tavora (8 November 2010). Practical Cardiovascular Pathology. Lippincott Williams & Wilkins. pp. 96–. ISBN 978-1-60547-841-8. 14. ^ Luciani, Giovanni Battista; Montalbano, Giuseppe; Casali, Gianluca; Mazzucco, Alessandro (2000). "Predicting long-term functional results after myocardial revascularization in ischemic cardiomyopathy". The Journal of Thoracic and Cardiovascular Surgery. 120 (3): 478–489. doi:10.1067/mtc.2000.108692. ISSN 0022-5223. PMID 10962408. 15. ^ Falk, Erling; Shah, Prediman; Feyter, Pim de (2007-03-28). Ischemic Heart Disease. CRC Press. p. 226. ISBN 9781840765151. 16. ^ Cai, Lu; Keller, Bradley B (2014-01-03). "Cardiac regeneration and diabetes". Regenerative Medicine Research. 2 (1): 1. doi:10.1186/2050-490X-2-1. ISSN 2050-490X. PMC 4422323. PMID 25984329. 17. ^ Iskandrian, Abdulmassih S.; Helfeld, Hope; Lemlek, Joseph; Lee, Jaetae; Iskandrian, Basil; Heo, Jaekyeong (1992). "Differentiation between primary dilated cardiomyopathy and ischemic cardiomyopathy based on right ventricular performance". American Heart Journal. 123 (3): 768–773. doi:10.1016/0002-8703(92)90518-Z. ISSN 0002-8703. PMID 1539529. 18. ^ Hunt, S. A. (20 September 2005). "ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society". Circulation. 112 (12): 1825–1852. doi:10.1161/CIRCULATIONAHA.105.167587. 19. ^ Maxey, Thomas S; Reece, T.Brett; Ellman, Peter I; Butler, Paris D; Kern, John A; Tribble, Curtis G; Kron, Irving L (2004). "Coronary artery bypass with ventricular restoration is superior to coronary artery bypass alone in people with ischemic cardiomyopathy". The Journal of Thoracic and Cardiovascular Surgery. 127 (2): 428–434. doi:10.1016/j.jtcvs.2003.09.024. ISSN 0022-5223. PMID 14762351. 20. ^ Louie HW, Laks H, Milgalter E, Drinkwater DC, Hamilton MA, Brunken RC, Stevenson LW (November 1991). "Ischemic cardiomyopathy. Criteria for coronary revascularization and cardiac transplantation". Circulation. 84 (5 Suppl): III290–III295. PMID 1934422. 21. ^ O’Connor, Christopher M; Velazquez, Eric J; Gardner, Laura H; Smith, Peter K; Newman, Mark F; Landolfo, Kevin P; Lee, Kerry L; Califf, Robert M; Jones, Robert H (2002). "Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank)". The American Journal of Cardiology. 90 (2): 101–107. doi:10.1016/S0002-9149(02)02429-3. ISSN 0002-9149. PMID 12106836. 22. ^ Velazquez, Eric J.; Williams, Judson B.; Yow, Eric; Shaw, Linda K.; Lee, Kerry L.; Phillips, Harry R.; O’Connor, Christopher M.; K.Smith, Peter; Jones, Robert H. (2012-02-01). "Long-term Survival of Patients with Ischemic Cardiomyopathy Treated by CABG versus Medical Therapy". The Annals of Thoracic Surgery. 93 (2): 523–530. doi:10.1016/j.athoracsur.2011.10.064. ISSN 0003-4975. PMC 3638256. PMID 22269720. 23. ^ Elefteriades, John A; Morales, David L.S; Gradel, Christophe; Tollis, George; Levi, Evelyn; Zaret, Barry L (1997). "Results of Coronary Artery Bypass Grafting by a Single Surgeon Patients With Left Ventricular Ejection Fractions ≤30%". The American Journal of Cardiology. 79 (12): 1573–1578. doi:10.1016/S0002-9149(97)00201-4. ISSN 0002-9149. PMID 9202343. ## Further reading[edit] * Likoff, Jessup Mariell, Chandler Sheryl L., Kay Harold R. (1987). "Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy". The American Journal of Cardiology. 59 (6): 634–638. doi:10.1016/0002-9149(87)91183-0. PMID 3825904.CS1 maint: multiple names: authors list (link) * Carmeliet Peter; et al. (1999). "Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188". Nature Medicine. 5 (5): 495–502. doi:10.1038/8379. PMID 10229225. * Menasché Philippe; et al. (2008). "The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial first randomized Placebo-controlled study of myoblast transplantation". Circulation. 117 (9): 1189–1200. doi:10.1161/circulationaha.107.734103. PMID 18285565. * Beltrami Carlo Alberto; et al. (1994). "Structural basis of end-stage failure in ischemic cardiomyopathy in humans". Circulation. 89 (1): 151–163. doi:10.1161/01.cir.89.1.151. PMID 8281642. ## External links[edit] Classification D * ICD-10: I25.5 Scholia has a topic profile for Ischemic cardiomyopathy. * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline * v * t * e Cardiovascular disease (heart) Ischaemic Coronary disease * Coronary artery disease (CAD) * Coronary artery aneurysm * Spontaneous coronary artery dissection (SCAD) * Coronary thrombosis * Coronary vasospasm * Myocardial bridge Active ischemia * Angina pectoris * Prinzmetal's angina * Stable angina * Acute coronary syndrome * Myocardial infarction * Unstable angina Sequelae * hours * Hibernating myocardium * Myocardial stunning * days * Myocardial rupture * weeks * Aneurysm of heart / Ventricular aneurysm * Dressler syndrome Layers Pericardium * Pericarditis * Acute * Chronic / Constrictive * Pericardial effusion * Cardiac tamponade * Hemopericardium Myocardium * Myocarditis * Chagas disease * Cardiomyopathy * Dilated * Alcoholic * Hypertrophic * Tachycardia-induced * Restrictive * Loeffler endocarditis * Cardiac amyloidosis * Endocardial fibroelastosis * Arrhythmogenic right ventricular dysplasia Endocardium / valves Endocarditis * infective endocarditis * Subacute bacterial endocarditis * non-infective endocarditis * Libman–Sacks endocarditis * Nonbacterial thrombotic endocarditis Valves * mitral * regurgitation * prolapse * stenosis * aortic * stenosis * insufficiency * tricuspid * stenosis * insufficiency * pulmonary * stenosis * insufficiency Conduction / arrhythmia Bradycardia * Sinus bradycardia * Sick sinus syndrome * Heart block: Sinoatrial * AV * 1° * 2° * 3° * Intraventricular * Bundle branch block * Right * Left * Left anterior fascicle * Left posterior fascicle * Bifascicular * Trifascicular * Adams–Stokes syndrome Tachycardia (paroxysmal and sinus) Supraventricular * Atrial * Multifocal * Junctional * AV nodal reentrant * Junctional ectopic Ventricular * Accelerated idioventricular rhythm * Catecholaminergic polymorphic * Torsades de pointes Premature contraction * Atrial * Junctional * Ventricular Pre-excitation syndrome * Lown–Ganong–Levine * Wolff–Parkinson–White Flutter / fibrillation * Atrial flutter * Ventricular flutter * Atrial fibrillation * Familial * Ventricular fibrillation Pacemaker * Ectopic pacemaker / Ectopic beat * Multifocal atrial tachycardia * Pacemaker syndrome * Parasystole * Wandering atrial pacemaker Long QT syndrome * Andersen–Tawil * Jervell and Lange-Nielsen * Romano–Ward Cardiac arrest * Sudden cardiac death * Asystole * Pulseless electrical activity * Sinoatrial arrest Other / ungrouped * hexaxial reference system * Right axis deviation * Left axis deviation * QT * Short QT syndrome * T * T wave alternans * ST * Osborn wave * ST elevation * ST depression * Strain pattern Cardiomegaly * Ventricular hypertrophy * Left * Right / Cor pulmonale * Atrial enlargement * Left * Right * Athletic heart syndrome Other * Cardiac fibrosis * Heart failure * Diastolic heart failure * Cardiac asthma * Rheumatic fever *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Ischemic cardiomyopathy

c0349782

wikipedia

https://en.wikipedia.org/wiki/Ischemic_cardiomyopathy

{"wikidata": ["Q12075432"]}

Satoyoshi syndrome Other namesKomuragaeri disease SpecialtyImmunology Satoyoshi syndrome, also known as Komura-Guerri syndrome, is a rare progressive disorder of presumed autoimmune cause, characterized by painful muscle spasms, alopecia, diarrhea, endocrinopathy with amenorrhoea and secondary skeletal abnormalities.[1] The syndrome was first reported in 1967 by Eijiro Satoyoshi and Kaneo Yamada in Tokyo, Japan. To this date, fewer than 50 cases worldwide have been reported for the Satoyoshi syndrome.[2] People with the syndrome typically develop symptoms of the illness at a young age, usually between the age of six and fifteen years old. The initial symptoms are muscle spasms in the legs and alopecia, also known as baldness. The spasms are painful and progressive and their frequency varies from 1 or 2 to 100 per day, each lasting a few minutes. It can be sufficiently severe to produce abnormal posturing of the affected limbs, particularly the thumbs. With progression the illness involves the pectoral girdle and trunk muscles and finally the masseters and temporal muscles. The spasms usually spare the facial muscles. Severe spasms can interfere with respiration and speech. During an attack-free period, non-stimulus-sensitive myoclonus can occur in the arms, legs and neck. Diarrhea occurs in the first 2–3 years with intolerance to carbohydrate and high glucose diets. Endocrinopathy manifests as amenorrhea and hypoplasia of the uterus. Affected children fail to attain height after 10–12 years of age.[3] The syndrome is not known to be a primary cause of mortality, but some patients have died as a result of secondary complications, such as respiratory failure and malnourishment. In one 6-year-old patient antibodies to GABA-producing enzyme glutamate decarboxylase were detected.[4] ## See also[edit] * Stiff person syndrome ## References[edit] 1. ^ http://bioline.utsc.utoronto.ca/archive/00001184/01/ni04023.pdf 2. ^ https://www.jstage.jst.go.jp/article/naika1913/91/8/91_8_2325/_pdf(in Japanese)) 3. ^ Satoyoshi syndrome neurologyindia.com 4. ^ Drost G, Verrips A, Hooijkaas H, Zwarts M (March 2004). "Glutamic acid decarboxylase antibodies in Satoyoshi syndrome". Ann. Neurol. 55 (3): 450–1. doi:10.1002/ana.20007. PMID 14991831. S2CID 40178572. ## External links[edit] Classification D * OMIM: 600705 * MeSH: C536616 External resources * Orphanet: 3130 *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Satoyoshi syndrome

c1833454

wikipedia

https://en.wikipedia.org/wiki/Satoyoshi_syndrome

{"gard": ["160"], "mesh": ["C536616"], "umls": ["C1833454"], "orphanet": ["3130"], "wikidata": ["Q7426433"]}

Attenuated familial adenomatous polyposis Other namesAttenuated familial polyposis coli SpecialtyOncology Attenuated familial adenomatous polyposis is a form of familial adenomatous polyposis, a cancer syndrome. It is a pre-malignant disease that can develop into colorectal cancer. A patient will have fewer than a hundred polyps located typically in right side of the colon. Cancer might develop as early as the age of five, though typically presents later than classical FAP.[1] ## See also[edit] * Familial adenomatous polyposis * Birt–Hogg–Dubé syndrome * Cowden syndrome * Cronkhite–Canada syndrome * Juvenile polyposis * MUTYH * Peutz–Jeghers syndrome ## References[edit] 1. ^ Herold, Gerd (2012). Innere Medizin : eine vorlesungsorientierte Darstellung (2012 ed.). Köln: Herold. ISBN 978-3-9814660-1-0. ## External links[edit] Classification D * ICD-10: D12.6 * MeSH: C538265 C538265, C538265 External resources * Orphanet: 220460 This article about a neoplasm is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Attenuated familial adenomatous polyposis

c2674616

wikipedia

https://en.wikipedia.org/wiki/Attenuated_familial_adenomatous_polyposis

{"gard": ["8532"], "mesh": ["C538265"], "umls": ["C2674616"], "orphanet": ["220460"], "wikidata": ["Q4818237"]}

## Clinical Features Blom et al. (1981) reported a newborn girl with hypotonic myopathy, severe brain damage, and poor growth. On a carbohydrate-rich diet, she had urinary excretion of hexanoic acid, including 2-ethyl-3-keto-hexanoic acid, 2-ethyl-3-hydroxy-hexanoic acid, and 2-ethyl-hexanedioic acid. Liver biopsy showed deficient activity of acetyl-CoA carboxylase (ACACA; 200350); fibroblasts showed about 10% of normal activity. Blom et al. (1981) concluded that the patient had an inborn error of de novo fatty acid synthesis. INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth MUSCLE, SOFT TISSUES \- Hypotonia \- Myopathy NEUROLOGIC Central Nervous System \- Severe brain damage LABORATORY ABNORMALITIES \- Urinary excretion of 2-ethyl-3-keto-hexanoic acid \- Urinary excretion of 2-ethyl-3-hydroxy-hexanoic acid \- Urinary excretion of 2-ethyl-hexanedioic acid \- Decreased acetyl-CoA carboxylase activity MISCELLANEOUS \- Onset in the perinatal period \- One patient has been reported (as of April 2011) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

ACETYL-CoA CARBOXYLASE DEFICIENCY

c0268603

omim

https://www.omim.org/entry/613933

{"mesh": ["C562678"], "omim": ["613933"], "synonyms": ["Alternative titles", "ACACA DEFICIENCY", "ACC1 DEFICIENCY"]}

A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-68 (MRT68) is caused by homozygous mutation in the TRMT1 gene (611669) on chromosome 19p13. Clinical Features Najmabadi et al. (2011) reported a consanguineous Iranian family (M300) in which 5 individuals had nonsyndromic moderate to severe impaired intellectual development. Clinical details were limited. A subsequent report by Davarniya et al. (2015) included the clinical features of 2 patients in family M300, noting that they had mild dysmorphic facial features with protruding ears, narrow palpebral fissures, and broad eyebrows. They also had involvement of the extremities, with pes planus and onset of progressive spasticity in the lower limbs during adolescence. Brain imaging reportedly showed cerebellar atrophy and an enlarged fourth ventricle. Davarniya et al. (2015) reported 3 adult brothers, born of consanguineous Iranian parents (family 9000114), with MRT68. They had low birth weight and overall poor growth, global developmental delay with delayed walking, moderately delayed intellectual development (IQ range 55-70), and delayed speech until 4 to 6 years of age. Mild dysmorphic features, such as synophrys, broad nasal bridge, and hypoplastic maxilla, were also present. One patient had hearing loss. All also had muscle weakness in the upper and lower limbs. Brain imaging did not reveal significant abnormalities. Blaesius et al. (2018) reported 4 patients from 2 unrelated Pakistani families with MRT68. The patients presented at birth with microcephaly and later showed impaired intellectual development. Three adult sibs from 1 family did not have motor involvement, whereas the single patient from the second family was more severely affected with motor and speech delay and hypotonia. Two of the adult sibs and the singleton patient had progressive microcephaly (-4 to -4.9 SD). All had seizures. Brain imaging of the singleton patient showed generalized white matter volume loss, periventricular leukomalacia, and isolated inferior vermis hypoplasia. Inheritance The transmission pattern of MRT68 in the family reported by Davarniya et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of a consanguineous Iranian family (M300) with MRT68, Najmabadi et al. (2011) identified a homozygous frameshift mutation in the TRMT1 gene (611669.0001). The family was part of a large cohort of 136 consanguineous families with intellectual disability who underwent genetic analysis. Functional studies of the variant were not performed. In 3 adult brothers, born of consanguineous Iranian parents (family 9000114), with MRT68, Davarniya et al. (2015) identified a homozygous frameshift mutation in the TRMT1 gene (611669.0003). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in 100 Iranian controls. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in a loss of function. In 4 patients from 2 unrelated consanguineous Pakistani families with MRT68, Blaesius et al. (2018) identified homozygous loss of function mutations in the TRMT1 gene (611669.0001 and 611669.0002). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies of the variant and studies of patient cells were not performed. INHERITANCE \- Autosomal recessive GROWTH Weight \- Low birth weight Other \- Poor overall growth HEAD & NECK Head \- Microcephaly, congenital, progressive (-4.5 SD) (in some patients) Face \- Dysmorphic facial features, mild, variable (in some patients) \- Hypoplastic maxilla Eyes \- Synophrys \- Narrow palpebral fissures \- Broad eyebrows Nose \- Broad nasal bridge SKELETAL Feet \- Pes planus (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia (in some patients) \- Muscle weakness, lower limbs (in some patients) NEUROLOGIC Central Nervous System \- Global developmental delay \- Impaired intellectual development \- Speech delay \- Delayed walking \- Spasticity of the lower limbs (in some patients) \- Seizures (in some patients) \- Cerebellar atrophy (in some patients) \- Generalized white matter volume loss (in some patients) \- Periventricular leukomalacia (in some patients) MISCELLANEOUS \- Onset in infancy \- Variable phenotype \- Some patients have no motor involvement MOLECULAR BASIS \- Caused by mutation in the tRNA methyltransferase 1 gene (TRMT1, 611669.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 68

None

omim

https://www.omim.org/entry/618302

{"omim": ["618302"], "synonyms": ["Alternative titles", "MENTAL RETARDATION, AUTOSOMAL RECESSIVE 68"]}

A rare, biliary tract disease characterized by progressive obliterative cholangiopathy of the intra- and extrahepatic bile ducts, occuring in the embryonic/ perinatal period, leading to severe and persistent neonatal jaundice and acholic stool. ## Epidemiology Biliary atresia (BA) prevalence at birth is 1/ 15,000-19,000 in Europe and North America. ## Clinical description Diagnosis is mostly made at 2-6 weeks of age, presenting with cholestasis, jaundice, acholia and possibly choluria and hepatomegaly, and sometimes vitamin K deficiency induced bleedings. Conjugated hyperbilirubinemia associated with an increase in γ-glutamyltransferase (GGT) are biochemical signs of the disease. The pathology is characterized by an ongoing inflammatory process of the entire biliary tree, although the disease is defined as an irreversible closure/ atresia of the extrahepatic bile ducts. In 10-20% of cases, biliary atresia is associated with other malformations (syndromic biliary atresia). ## Etiology The etiology is yet to be explained, but it is believed that it can be the result of the interaction of genetic, environmental, immune, and infectious factors, individually or in combination. ## Diagnostic methods Preoperative evaluation may include abdominal ultrasound, hepatobiliary scintigraphy, percutaneous liver biopsy, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography (MRCP). However, the definitive diagnosis is confirmed only by cholangiography. ## Differential diagnosis The differential diagnosis include other causes of neonatal cholestasis, for example infections, Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familiar intrahepatic cholestasis (PFIC) and hormonal deficiencies. ## Antenatal diagnosis Signs of biliary atresia on prenatal ultrasonography has rarely been reported. ## Genetic counseling The disease is not yet identified to be hereditary. The genetic counseling is therefore not possible. ## Management and treatment Kasai portoenterostomy is the gold standard treatment, consisting in total extraction of the hilar fibrosis and subsequent biliary-enteric anastomosis, with favorable results in a maximum of 50% of cases, in which there is total restitution of the biliary drainage and normalization of total bilirubin levels. ## Prognosis The main prognostic factors to short- and long-term survival after surgery include age at surgery, type of biliary atresia, and experience of the center. Out of the possible complications, the most common are cholangitis, portal hypertension, and ongoing deterioration of the liver function with cirrhosis, leading to end-stage failure. Early liver transplantation is required in about 50% of the cases. Very long term survival with native liver decreases to about 25%. * European Reference Network *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Isolated biliary atresia

c0005411

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=30391

{"gard": ["12010"], "mesh": ["D001656"], "omim": ["210500"], "umls": ["C0005411"], "icd-10": ["Q44.2"], "synonyms": ["Isolated atresia of bile ducts", "Non-syndromic biliary atresia"]}

Kenya has a severe, generalized HIV epidemic, but in recent years, the country has experienced a notable decline in HIV prevalence, attributed in part to significant behavioral change and increased access to ART(antiretroviral drugs). Adult HIV prevalence is estimated to have fallen from 10 percent in the late 1990s to about 4.8 percent in 2017.[1] Women face considerably higher risk of HIV infection than men, and also experience a shorter life expectancy due to HIV/AIDS. The 7th edition of AIDS in Kenya reports an HIV prevalence rate of eight percent in adult women and four percent in adult men. Populations in Kenya that are especially at risk include injecting drug users and people in prostitution, whose prevalence rates are estimated at 53 percent and 27 percent, respectively. Men who have sex with men (MSM) are also at risk at a prevalence of 18.2%.[2] Other groups also include discordant couples (where one partner is infected and the other is not) however successful ARV-treatment will prevent transmission. Other groups at risk are prison communities, uniformed forces, and truck drivers.[3] ## Contents * 1 History * 2 Overview of the HIV epidemic * 3 Social outlook * 3.1 LGBTQ+ * 3.2 Adolescents * 3.3 Sex work * 4 Current status * 5 Cost * 5.1 Low Cost Antiretroviral Drugs * 6 Response * 6.1 HTC * 6.2 Condom Availability * 6.3 Education * 6.4 PMTCT * 6.5 VMMC, Harm Reduction, and PrEP * 7 See also * 8 References * 9 External links ## History[edit] The following will be a timeline of the major events that have led up to today in the HIV/AIDS epidemic in Kenya from 1984-2018.[4] 1984: First case of HIV found in Kenya[4] 1985: Sex workers were involved in 26 new recorded cases of HIV[4] 1985: The condition is still a mystery in Kenya[4] 1986: There is a mass denial of the disease being a problem[4] 1987: A study was performed on the unique women from Majengo slum in Nairobi, who were "immune" to AIDS[4] 1988: HIV prevalence is now at 3,000 cases[4] 1990: Prevalence rises to 2.5% of the population as the government is still in denial[4] 1995: By 1995, the death toll rose to about 200,000 people[4] 1998: Prevalence rate is at 9.8%[4] 2003: Prevalence rate drops to 6.7%[4] 2003: Public sector releases low cost ARVs[4] 2005: Around 65,000 HIV positive individuals in Kenya are on ARVs[4] 2012: Prevalence has dropped to 5.6%, but Kenya still has the 4th largest HIV epidemic[4] ## Overview of the HIV epidemic[edit] Here is a brief overview of the HIV epidemic in the country as reported by the Ministry of Education in June 2014, as well as the UNAIDS report on Kenya for 2017.[5][1] * 53,000 Kenyans were infected with HIV In 2017. * 8,000 children, 27,000 women, and 18,000 men were infected with HIV in 2017. * 65% of new HIV infections occur in 9 out of 47 counties.[6] County HIV Prevalence (%) Homa Bay 25.7 Siaya 23.7 Kisumu 19.3 Migori 14.7 Kisii 8 Turkana 7.6 Nairobi 6.8 Busia 6.8 Nyamira 6.4 * Every year, 21% of new adult HIV infections occur among young women aged 15–24. * In 2017, 1.5 million Kenyans were living with HIV. * In 2017, 110,000 children were living with HIV. * 63% of men and 80% of women know their HIV status. ## Social outlook[edit] ### LGBTQ+[edit] As the LGBTQ+ community has always been part of the fight against HIV/AIDS in all countries, the same has happened in Kenya. Although MSMs and other forms of same-sex contact are not the main risk group or cause of HIV/AIDS in Kenya, they have been a big proponent due to the laws that have been put in place by the country's government. Homosexuality is currently illegal in Kenya, allowing the government to 595 cases of homosexuality from 2010-2014. While MSMs and members of the LGBTQ+ community already face discrimination on a regular basis, they are being denied treatment due to their identity and the penal code in many places in Kenya.[7] However, recently, activist groups have been able to challenge the constitutionality of the laws that are in place, resulting in the government contemplating if they should be repealed. This advance happened in 2016, and currently the verdict has not come in about the constitutionality of the penal code that is in place with respect to this community. Victory has been won in other places that had laws that discriminated against the LGBTQ+ community, so the activists have a positive outlook on this subject at this point in time.[7] ### Adolescents[edit] With adolescents being a big risk group in Kenya, society has molded the outlook of this group and how they interact with HIV/AIDS. There are many social stigmas involved with people aged 15-19, as they go through harsh environments in schools and in the community. HIV and AIDS in school is viewed as a killer disease that is a sign of sexual immorality. Many adolescents feel afraid to disclose their status, due to the stigma that is behind it. Fear is also found in walking into health centers and asking about HIV/AIDS, due to the conception that health workers will look down on you and your condition.[8] Social media has also provided adolescents in Kenya with illegitimate information about the disease, prevention of the disease, and overall outlook. While the main fear is found in public shaming or judging, another problem is that adolescents are not represented in policy very well, compared to that of children and adults. Economic burdens that are placed on adolescents that do not have parents to provide the means for their education and wellbeing is another problem for the group. Sometimes, adolescents are forced into being sex workers to provide for themselves, resulting in an increased risk for HIV infection.[8] ### Sex work[edit] Sex workers have the highest prevalence among the risk groups of HIV/AIDS in Kenya. It has been reported that 29.3% of sex workers have HIV. The main problem within this community is the fear of coming forward about being raped or abused, because it could lead to prosecution for being a prostitute. Therefore, sex workers are less likely to go to anyone for help because of this fear. Being prosecuted and arrested can lead to an interruption in HIV treatment.[9] ## Current status[edit] The Kenyan Ministry of Health published a report on June 2014 called Kenya HIV Prevention Revolution Road Map. The road map aims to dramatically strengthen HIV prevention, with the ultimate goal of reducing new HIV infections to zero by 2030. The following observations and conclusions were outlined:[5] * Sexual transmission accounts for 93.7% of all new HIV infections (MOT, 2008). * The HIV epidemic in Kenya exhibits extreme geographical and gender disparities. National estimates and modelling indicate that 65% of new adult infections occur in nine of the 47 Counties. There is higher prevalence among women at 7.6% compared to men at 5.6%. There is a treatment gap of over 99,500 women and 64,900 men, in need of ART but not currently receiving treatment. ART coverage is 77% in eligible women compared to 80% in men. * Key populations contribute a disproportionately high number of new HIV infections annually despite their small population size. According to the MOT 2008, although these populations represent less than 2% of the general population, they contribute a third of all new HIV infections. Key populations in Kenya include sex workers, men who have sex with men (MSM) and people who inject drugs. Additionally, there are geographical disparities in the distribution of key populations across the Counties. * A recent development in April 2018 shows Kenya receiving funding from the Children's investment Fund Foundation to buy ARVs for children in the country. The country received 400 million Kenyan shillings after the 38 billion shillings was not enough to cover all the risk groups involved in the epidemic. While the grant for 38 billion shillings was given by the Global Fund to cover a broad spectrum of diseases including tuberculosis and malaria, the new grant has been given specifically for treatment of children with HIV. This is due to the fact that about 120,000 children, ages of fourteen and under, are living with HIV. As of 2012, Kenya has received about 100 billion shillings in funding over the span of 19 grants given by various organizations.[10] * As of September 2018, adolescents are a high risk group in Kenya to be infected by HIV. Nearly 106,000 adolescents, aging from 15 to 19, are living with HIV. This trend is on the rise due to the stigmatization of HIV/AIDS within adolescent communities and society. [8] ## Cost[edit] ### Low Cost Antiretroviral Drugs[edit] ART was introduced to Kenya in the late 90s when the treatment was initially being rolled out. However, they did not start receiving low cost drugs until around 2003. [4] Costs continued to decline, and with enough donor money, more than a million patients receive ART for free through the government. Recently, Kenyans with HIV got access to a high end drug for cheap due to an international deal. The cost per year for this drug treatment is US$75 and is a big improvement as it combines some drugs together to make the treatment plan cheaper and easier for patients living with HIV. This drug has been accessible in high income countries since 2014, but the new deal has placed the drug in middle and low income countries.[11] ## Response[edit] During the initial outbreak of AIDS in the 80s, the Kenyan government stayed away from discussions about how big of a problem there was with HIV/AIDS in the country. By 1993, statements were finally made about the problem and how the situation should have been addressed sooner. Kenya could not afford to lose so many skilled workers to HIV/AIDS when there was currently no treatment for it. The response and plan to reduce the amount of HIV infections has been more extensive going into the new century and currently.[12] ### HTC[edit] HIV testing and counseling (HTC) has been one response to the HIV/AIDS crisis in Kenya. The government has encouraged getting tested and for people to be more open about the diagnosis so it can be addressed appropriately. Self testing kits for low cost have been introduced over recent years, along with community based testing and door-to-door campaigns. In 2008, only 860,000 people were being annually tested for HIV, compared to 9.9 million people that are being tested annually now. [9] ### Condom Availability[edit] Even though condom use wasn't endorsed by the Kenyan government until 2001, the rate of condom usage has gradually increased ever since. Free condoms have been distributed throughout different communities, including the sex workers community. This has decreased unprotected sex, which is critical in lowering new HIV infections. [9] ### Education[edit] Education about HIV/AIDS has been in the school curriculum since 2003, and it has been effective in increasing knowledge within children about the disease. There has been some controversy about the ethics of teaching students about sexual health, due to the fear that it would encourage young people to have sex. However, rates of new HIV infections have said otherwise. Mass media campaigns have also been done to educate people about HIV/AIDS. [9] ### PMTCT[edit] Preventing mother to child transmission (PMTCT) has also been a big step in preventing the spread of HIV/AIDS. The country's dedication to eliminating this type of transmission has led to a drop of children born with HIV from 12,000 children in 2010 to 6,600 in 2015. Male partners have also been encouraged to take part in this type of treatment, by getting tested along with the soon-to-be mother.[9] ### VMMC, Harm Reduction, and PrEP[edit] Voluntary medical male circumcision (VMMC) was implemented as an option in 2008 in Kenya as a prevention method. By 2016, 92% of men in Kenya are circumcised.[9] Harm reduction is the distribution of clean needles and syringes along with counseling and medically assisted treatment with methadone, implemented by the government in 2012. The amount of Intravenous drug users that are using clean needles now is up to 90% compared to the 51% in 2012.[9] Pre-exposure prophylaxis has been an ongoing trend in Kenya, as HIV negative people have been receiving ART to prevent against any future infection of HIV. It is being offered for people who are in high risk groups that have an ongoing risk of HIV infection.[9] ## See also[edit] * AIDS pandemic * HIV/AIDS in Africa * Sex for Fish ## References[edit] 1. ^ a b "UNAIDS: Kenya fact sheet". 2017. 2. ^ "UNAIDS Data Book 2017" (PDF). 3. ^ "Kenya ranked fourth worldwide in HIV Infections". August 20, 2014. 4. ^ a b c d e f g h i j k l m n o timeline. "HIV: past, present and future". www.tiki-toki.com. Retrieved 2018-10-30. 5. ^ a b "Kenya_HIV_Prevention_Revolution_Road_Map" (PDF). 6. ^ "Counties With Highest HIV Infections - Report - Kenyans.co.ke". Kenyans.co.ke. Retrieved 2018-11-09. 7. ^ a b "THE REPEAL OF THE ANTI HOMOSEXUALITY LAWS IN KENYA". Kuchu Times. 2018-09-28. Retrieved 2018-10-30. 8. ^ a b c Africa, Science. "HIV: Kenyan Adolescents Hardest Hit | Science Africa". scienceafrica.co.ke. Retrieved 2018-10-30. 9. ^ a b c d e f g h "HIV and AIDS in Kenya". AVERT. 2015-07-21. Retrieved 2018-10-30. 10. ^ "Kenya gets Sh400m to buy ARVs for children". The Star, Kenya. Retrieved 2018-10-30. 11. ^ Jamah, Ally. "Kenyans to access new, highly-effective HIV drugs at lower prices". The Standard. Retrieved 2018-10-30. 12. ^ Lorch, Donatella. "After Years of Ignoring AIDS Epidemic, Kenya Has Begun Facing Up to It". Retrieved 2018-10-30. ## External links[edit] * HIV and AIDS in Kenya * Timeline of HIV and AIDS in Kenya * v * t * e HIV/AIDS in Africa Sovereign states * Algeria * Angola * Benin * Botswana * Burkina Faso * Burundi * Cameroon * Cape Verde (Cabo Verde) * Central African Republic * Chad * Comoros * Democratic Republic of the Congo * Republic of the Congo * Djibouti * Egypt * Equatorial Guinea * Eritrea * Eswatini (Swaziland) * Ethiopia * Gabon * The Gambia * Ghana * Guinea * Guinea-Bissau * Ivory Coast (Côte d'Ivoire) * Kenya * Lesotho * Liberia * Libya * Madagascar * Malawi * Mali * Mauritania * Mauritius * Morocco * Mozambique * Namibia * Niger * Nigeria * Rwanda * São Tomé and Príncipe * Senegal * Seychelles * Sierra Leone * Somalia * South Africa * South Sudan * Sudan * Tanzania * Togo * Tunisia * Uganda * Zambia * Zimbabwe States with limited recognition * Sahrawi Arab Democratic Republic * Somaliland Dependencies and other territories * Canary Islands / Ceuta / Melilla (Spain) * Madeira (Portugal) * Mayotte / Réunion (France) * Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by region *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

HIV/AIDS in Kenya

None

wikipedia

https://en.wikipedia.org/wiki/HIV/AIDS_in_Kenya

{"wikidata": ["Q5629852"]}

A rare mandibulofacial dysostosis characterized by the association with scalp alopecia and sparse eyebrows and eyelashes. Craniofacial dysmorphic features include zygomatic and mandibular dysplasia or hypoplasia, cleft palate, micrognathia, dental anomalies, auricular dysmorphism, and eyelid anomalies, among others. Patients may experience limited jaw mobility, glossoptosis, upper airway obstruction, and conductive hearing loss. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Mandibulofacial dysostosis with alopecia

c4225349

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443995

{"omim": ["616367"], "icd-10": ["Q75.4"], "synonyms": ["MFDA"]}

A number sign (#) is used with this entry because of evidence that hyperglycinuria can be caused by heterozygous mutation in the SLC36A2 gene (608331). Description The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG) (summary by Broer et al., 2008). A phenotype of combined glucosuria and glycinuria has been described (see 138070). Clinical Features De Vries et al. (1957) found hyperglycinuria in a grandmother, her daughter, and 2 granddaughters in an Ashkenazi Jewish kindred. The grandmother had had renal colic, and renal oxalate stones were demonstrated in the 2 granddaughters. This family is apparently unique for the association of oxalate stones. It was plausibly suggested by Scriver (1968) that the glycinuria trait observed in these families was the heterozygous state of iminoglycinuria (242600), a disorder that had been described several times in Ashkenazi families (Tancredi et al., 1970). Adams and Nance (1967) described a brother and sister with paroxysmal tachycardia, hypertension, syncope and seizures, associated with dominantly inherited microphthalmia, cataracts, hyperglycinuria, and renal stones. A disturbance in glycine metabolism was postulated. Greene et al. (1973) reported an Ashkenazi family in which the father and 2 sons had hyperglycinuria. The proband was discovered when he was studied as a normal volunteer. The father had a history compatible with renal colic but had not been known to pass stones. One son had a lifelong impairment of the sense of smell. Plasma glycine concentrations were normal. Intravenous proline infusion in 1 son showed a normal maximal transport rate for proline, but there was marked splay in the renal tubular titration curve for proline reabsorption, considered consistent with a 'Km' mutation affecting proline binding. Greene et al. (1973) concluded that the mutation affecting glycine-proline-hydroxyproline renal transport in their family is different from that in previously described families. They suggested the designation iminoglycinuria type II. Broer et al. (2008) noted that the physiologic measurements reported by Greene et al. (1973) accurately described their own functional analysis of the SLC36A2 G87V mutation (608331.0001), which has the same maximum velocity but a change in affinity for proline compared to wildtype. Molecular Genetics Broer et al. (2008) studied 3 French Canadian and 4 Australian families, each with an index case previously identified from newborn urinary screening programs for iminoglycinuria (IG; 242600). IG was reconfirmed in all but 2 of the probands: in 2 of the Australian families, the probands had only persistent hyperglycinuria (HG). Broer et al. (2008) sequenced 5 known imino acid and glycine transporter candidates and found that the main contribution to IG and HG arose from defects in the gene encoding the proton amino acid transporter SLC36A2 (608331.0001 and 608331.0002), with a classic semidominant inheritance pattern in which 2 nonfunctional alleles conferred the IG phenotype whereas 1 nonfunctional allele was sufficient to confer the HG phenotype. Broer et al. (2008) noted that additional polymorphisms and mutations were identified in the affected individuals in the genes encoding the imino acid transporter SLC6A20 (605616), the putative glycine transporter SLC6A18 (610300), and the neutral amino acid transporter SLC6A19 (608893), and suggested that variation in these genes might also contribute to these phenotypes. Thus, IG and HG exhibit complex molecular explanations depending on a major gene and accompanying modifier genes. GU \- Renal colic \- Renal oxalate stones Lab \- Hyperglycinuria Inheritance \- Autosomal dominant ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

HYPERGLYCINURIA

c0543541

omim

https://www.omim.org/entry/138500

{"mesh": ["C563009"], "omim": ["138500"], "synonyms": ["Alternative titles", "GLYCINURIA WITH OR WITHOUT OXALATE UROLITHIASIS", "GLYCINURIA WITH OR WITHOUT OXALATE NEPHROLITHIASIS", "IMINOGLYCINURIA TYPE II"]}

For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641. Mapping To identify regions that are likely to harbor quantitative trait loci (QTLs) for body mass index, Feitosa et al. (2002) conducted an autosomal genome scan for BMI through use of a variance-components-based linkage analysis in families participating in the National Heart, Lung, and Blood Institute Family Heart Study. They found strong evidence for linkage on 7q32.3 in each of 2 samples and in the samples combined (see BMIQ1, 606641). In the analysis of the combined sample, evidence of linkage was also found on 13q14 with a lod score of 3.2 with marker D13S257. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 2

c1847733

omim

https://www.omim.org/entry/606643

{"omim": ["606643"]}

Osteopenia-myopia-hearing loss-intellectual disability-facial dysmorphism syndrome is characterised by severe hypertelorism, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, osteopaenia with frequent fractures, severe myopia, mild to moderate sensorineural hearing loss and mild intellectual deficit. It has been described in two brothers born to first-cousin parents. No chromosomal anomalies were detected. Transmission appears to be autosomal recessive or X-linked. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Osteopenia-myopia-hearing loss-intellectual disability-facial dysmorphism syndrome

None

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=91133

{"icd-10": ["Q87.5"], "synonyms": ["Osteopenia-myopia-deafness-intellectual disability-facial dysmorphism syndrome"]}

What follows is a list of all the athletes that have tested positive for a banned substance either during or before an Asian Games in which they competed. Any medals listed were revoked. ## Contents * 1 Asian Games * 1.1 1974 Tehran * 1.2 1994 Hiroshima * 1.3 1998 Bangkok * 1.4 2002 Busan * 1.5 2006 Doha * 1.6 2010 Guangzhou * 1.7 2014 Incheon * 1.8 2018 Jakarta–Palembang * 2 See also * 3 References ## Asian Games[edit] ### 1974 Tehran[edit] Main article: 1974 Asian Games Name NOC Sport Banned substance Medals Ref Oh Han-nam South Korea Volleyball (Men) [1] Masushi Ouchi Japan Weightlifting Stimulant (Men's 90 kg) (Men's snatch 90 kg) (Men's clean & jerk 90 kg) [2] Kim Joong-iI North Korea Weightlifting Stimulant (Men's 110 kg) (Men's snatch 110 kg) (Men's clean & jerk 110 kg) [3] ### 1994 Hiroshima[edit] Main article: 1994 Asian Games Name NOC Sport Banned substance Medals Ref Han Qing China Athletics Dihydrotestosterone (Women's 400 m hurdles) [4] Zhang Lei China Canoeing Dihydrotestosterone (Men's C-1 500 m) (Men's C-1 1000 m) (Men's C-2 500 m) [4] Qiu Suoren China Canoeing Dihydrotestosterone (Men's C-2 1000 m) [4] Wang Yan China Cycling Dihydrotestosterone (Women's sprint) [4] Sirisak Kadalee Thailand Football Stimulant [5] Fu Yong China Swimming Dihydrotestosterone (Men's 400 m individual medley) [6] Hu Bin China Swimming Dihydrotestosterone (Men's 50 m freestyle) [6] Lü Bin China Swimming Dihydrotestosterone (Women's 50 m freestyle) (Women's 200 m freestyle) (Women's 200 m individual medley) (Women's 4 × 100 m freestyle relay) (Women's 100 m freestyle) (Women's 100 m backstroke) [6] Xiong Guoming China Swimming Dihydrotestosterone (Men's 200 m freestyle) (Men's 200 m individual medley) (Men's 400 m individual medley) (Men's 4 × 200 m freestyle relay) (Men's 4 × 100 m freestyle relay) [6] Yang Aihua China Swimming Dihydrotestosterone (Women's 400 m freestyle) [6] Zhang Bin China Swimming Dihydrotestosterone (Men's 200 m butterfly) [6] Zhou Guanbin China Swimming Dihydrotestosterone (Women's 400 m freestyle) (Women's 800 m freestyle) [6] ### 1998 Bangkok[edit] Main article: 1998 Asian Games Name NOC Sport Banned substance Medals Ref Abdullah Sabt Ghulam United Arab Emirates Athletics Ephedrine [7] Fakhruddin Abdulmajid United Arab Emirates Karate Ephedrine (Men's kumite 75 kg) [7] Ayed Khawaldeh Jordan Weightlifting Triamterene [8] Jaber Al-Ajmi Kuwait Weightlifting Nandrolone [8] ### 2002 Busan[edit] Main article: 2002 Asian Games Name NOC Sport Banned substance Medals Ref Youssef El-Zein Lebanon Bodybuilding Missed the test (Men's +90 kg) [9] ### 2006 Doha[edit] Main article: 2006 Asian Games Name NOC Sport Banned substance Medals Ref Santhi Soundarajan India Athletics Male hormone (Women's 800 m) [10] Sayed Faisal Husain Bahrain Bodybuilding (Men's 70 kg) [11] Faez Abdul-Hassan Iraq Bodybuilding Nandrolone [12] Kim Myong-hun South Korea Bodybuilding (Men's 90 kg) [13] Salem Ghanem Al-Shamsi United Arab Emirates Bodybuilding [14] Kyi Kyi Than Myanmar Weightlifting Diuretic [12] Mya Sanda Oo Myanmar Weightlifting Metabolite (Women's 75 kg) [12] Elmira Ramileva Uzbekistan Weightlifting Stanozolol [12] Aleksandr Urinov Uzbekistan Weightlifting Cannabis [12] ### 2010 Guangzhou[edit] Main article: 2010 Asian Games Name NOC Sport Banned substance Medals Ref Suresh Sathya India Athletics Nandrolone [15] Ahmed Dheeb Qatar Athletics Testosterone (Men's discus throw) [16] Abdelnasser Awajna Palestine Athletics Norandrosterone [16] Masoud Rigi Iran Boxing Nandrolone [17] Shokir Muminov Uzbekistan Judo Methylhexanamine (Men's 81 kg) [18] Jakhongir Muminov Uzbekistan Wrestling Methylhexanamine [19] ### 2014 Incheon[edit] Main article: 2014 Asian Games Name NOC Sport Banned substance Medals Ref Betlhem Desalegn United Arab Emirates Athletics Biological passport abnormalities [20] Khurshed Beknazarov Tajikistan Football Methylhexanamine [21] Nouraddin Al-Kurdi Syria Karate Clenbuterol [22] Yi Sophany Cambodia Soft tennis Sibutramine [23] Park Tae-hwan South Korea Swimming Nebido (Men's 100 m freestyle) (Men's 200 m freestyle) (Men's 400 m freestyle) (Men's 4 × 100 m freestyle relay) (Men's 4 × 200 m freestyle relay) (Men's 4 × 100 m medley relay) [24] Mohammed Jassim Iraq Weightlifting Etiocholanolone [22] Tai Cheau Xuen Malaysia Wushu Sibutramine (Women's nanquan) [25] ### 2018 Jakarta–Palembang[edit] Main article: 2018 Asian Games Name NOC Sport Banned substance Medals Ref Kemi Adekoya Bahrain Athletics Stanozolol (Women's 400 m hurdles) (Mixed 4 × 400 m relay) [26] Sanjivani Jadhav India Athletics Probenecid [26] Nirmala Sheoran India Athletics Drostanolone and Metenolone [27] Kumush Yuldashova Uzbekistan Kurash Stanozolol (Women's 78 kg) [28] Pürevdorjiin Orkhon Mongolia Wrestling Stanozolol (Women's freestyle 62 kg) [29] Rüstem Nazarow Turkmenistan Wrestling Furosemide [30] ## See also[edit] * Asia portal * Sports portal * Doping at the Commonwealth Games * Doping at the Olympics ## References[edit] 1. ^ "South Korea's volleyball silver in the balance". The Straits Times. 18 September 1974. p. 22. Retrieved 9 January 2014. 2. ^ ""Return gold medals", order to 2 lifters". New Straits Times. 11 September 1974. p. 20. Retrieved 12 April 2013. 3. ^ "Doping: North Korea lifter may lose all". New Straits Times. 10 September 1974. p. 21. Retrieved 12 April 2013. 4. ^ a b c d "Chinese hand out long bans". The Independent. 21 December 1994. Retrieved 14 April 2013. 5. ^ "Results". The New York Times. Retrieved 8 January 2021. 6. ^ a b c d e f g "China ban seven swimmers for two years". New Straits Times. 8 December 1994. Retrieved 14 April 2013. 7. ^ a b "OCA in quandary over re-allocation of silver medal". Agence France-Presse. The Indian Express. 23 December 1998. Retrieved 13 April 2013. 8. ^ a b "Kuwait weightlifter Jaber al-Ajmi caught in doping test". Sadec. 19 December 1998. Archived from the original on 26 March 2016. Retrieved 13 April 2013. 9. ^ "Lebanese bodybuilder stripped of bronze". The Daily Times. Agence France-Presse. 8 October 2002. Archived from the original on 22 October 2012. Retrieved 13 April 2013. 10. ^ "Indian athlete fails gender test". BBC News. 18 December 2006. Retrieved 12 April 2013. 11. ^ "Bodybuilder Syafrizaldy gets Asiad silver". The Jakarta Post. 16 May 2007. Archived from the original on 7 June 2011. Retrieved 12 April 2013. 12. ^ a b c d e "From weightlifting to bodybuilding, fifth doping offense announced". Xinhua News Agency. 12 December 2006. Retrieved 13 April 2013. 13. ^ "Hong Kong Sports Institute Presented Cash Awards to Asian Games Bronze Medallist Lam Man-shing". Hong Kong Sports Institute. 22 May 2007. Archived from the original on 8 June 2010. Retrieved 12 April 2013. 14. ^ "2006 Asian Games". musclememory.com. Retrieved 24 April 2013. 15. ^ "Indian runner tests positive for doping". supersport.com. 5 December 2010. Archived from the original on 11 April 2013. Retrieved 14 April 2013. 16. ^ a b "2 Asian Games athletes fail drug test". ESPN. 25 January 2011. Retrieved 14 April 2013. 17. ^ "4 athletes banned after using enhancing drugs". iransportspress.com. Mehr News Agency. 22 February 2011. Archived from the original on 25 February 2011. Retrieved 14 April 2013. 18. ^ "Uzbek stripped of silver medal for doping". Reuters India. 19 November 2010. Retrieved 13 April 2013. 19. ^ "2nd Uzbek athlete fails doping test at Asian Games". Sports Illustrated. 24 November 2010. Retrieved 13 April 2013. 20. ^ Etchells, Daniel (23 October 2017). "Athletics Integrity Unit welcomes CAS decision to give UAE runner Desalegn two-year doping ban". Inside the Games. Retrieved 30 March 2019. 21. ^ "Malaysian wushu failed dope test". The Star. 26 September 2014. Retrieved 26 September 2014. 22. ^ a b "Iraq, Syria athletes banned from Asiad for doping". Yahoo. 1 October 2014. Retrieved 1 October 2014. 23. ^ "Second Doping Case Confirmed at Asian Games". Associated Press. 27 September 2014. Archived from the original on 4 March 2016. Retrieved 27 September 2014. 24. ^ "OCA adjusts Incheon Asian Games medal table". Olympic Council of Asia. 27 May 2015. Retrieved 31 July 2015.[permanent dead link] 25. ^ "Wushu exponent Cheau Xuen fails dope test". The Star. 30 September 2014. Retrieved 2 October 2014. 26. ^ a b "India in line for Asian Games mixed relay gold after ban on Kemi Adekoya". The Indian Express. 19 July 2019. Retrieved 21 July 2019. 27. ^ "Sprinter Nirmala Sheoran banned for 4 years, stripped of Asian titles". Hindustan Times. 19 July 2019. Retrieved 10 October 2019. 28. ^ "Doping Ban Asian Games 2018". International Kurash Association. 11 March 2019. Retrieved 21 July 2019. 29. ^ "Mongolian gold medallist tests positive". The Indian Express. 3 September 2018. Archived from the original on 12 September 2018. Retrieved 5 September 2018. 30. ^ "Asian Games 2018: Turkmenistan wrestler doping case puts wrestling under pressure". The Hindu. 24 August 2018. Retrieved 24 August 2018. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Doping at the Asian Games

None

wikipedia

https://en.wikipedia.org/wiki/Doping_at_the_Asian_Games

{"wikidata": ["Q17085227"]}

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Traumatic cardiac arrest" – news · newspapers · books · scholar · JSTOR (February 2012) (Learn how and when to remove this template message) Traumatic cardiac arrest Human heart SpecialtyCardiology, Emergency Medicine, Critical Care, Trauma Traumatic cardiac arrest (TCA) is a condition in which the heart has ceased to beat due to blunt or penetrating trauma, such as a stab wound to the thoracic area.[1] It is a medical emergency which will always result in death without prompt advanced medical care. Even with prompt medical intervention, survival without neurological complications is rare.[2] There are no definitive protocols in place in how to manage traumatic cardiac arrest, but certain people benefit from the use of a thoracotomy in order to gain access and repair damage from the injury.[3] Traumatic cardiac arrest is a complex form of cardiac arrest often derailing from Advanced Cardiac Life Support in the sense that the emergency team must first establish the cause of the traumatic arrest and reverse these effects, for example hypovolemia and haemorrhagic shock due to a penetrating injury. ## References[edit] 1. ^ Hunt PA, Greaves I, Owens WA (January 2006). "Emergency thoracotomy in thoracic trauma-a review". Injury. 37 (1): 1–19. doi:10.1016/j.injury.2005.02.014. PMID 16410079. 2. ^ Gräsner JT, Wnent J, Seewald S, et al. (2011). "Cardiopulmonary resuscitation traumatic cardiac arrest--there are survivors. An analysis of two national emergency registries". Critical Care (London, England). 15 (6): R276. doi:10.1186/cc10558. PMC 3388703. PMID 22108048. 3. ^ Cothren CC, Moore EE (2006). "Emergency department thoracotomy for the critically injured patient: Objectives, indications, and outcomes". World Journal of Emergency Surgery. 1: 4. doi:10.1186/1749-7922-1-4. PMC 1459269. PMID 16759407. * v * t * e Chest injury, excluding fractures Cardiac and circulatory system injuries * vascular: Traumatic aortic rupture * Thoracic aorta injury * heart: Myocardial contusion/Commotio cordis * Cardiac tamponade * Hemopericardium * Myocardial rupture Lung and lower respiratory tract injuries * Pneumothorax * Hemothorax * Hemopneumothorax * Pulmonary contusion * Pulmonary laceration * Tracheobronchial injury * Diaphragmatic rupture This article about an injury is a stub. You can help Wikipedia by expanding it. * v * t * e This article about a medical condition affecting the circulatory system is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Traumatic cardiac arrest

None

wikipedia

https://en.wikipedia.org/wiki/Traumatic_cardiac_arrest

{"wikidata": ["Q7835828"]}

A genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs) with onset during the third decade of life, characterized by dementia, seizures and loss of motor capacities, and sometimes associated with visual loss caused by retinal degeneration. ## Epidemiology Prevalence is unknown. ## Clinical description The clinical picture is characterized by onset with progressive myoclonic epilepsy or behavioral disturbances, dementia and extrapyramidal motor symptoms that appear at the age of 20-30 years. Vision loss is an uncommon feature and depends on the underlying genetic cause. ## Etiology The ANCL phenotype was originally designated as CLN4 disease, although the causative gene has not yet been identified. CLN4 may be inherited in an autosomal recessive (CLN4A) or autosomal dominant (CLN4B) manner. In addition, autosomal recessive ANCL may be caused by mutations in the following genes PPT1 (1p32; designated CLN1 and responsible for ANCL with vision loss) and CTSD (designated CLN10; 11p15.5). ## Diagnostic methods The diagnosis is based on the clinical picture, and enzymatic analysis (to detect deficiencies in palmitoyl-protein thioesterase 1 and cathepsin D, present in patients with PPT1 and CTSD mutations, respectively) and molecular testing. For some types, demonstration of storage material in tissues by electron microscopy is necessary for diagnosis. ## Differential diagnosis The differential diagnosis should include progressive myoclonus epilepsies (Unverricht-Lundborg disease, Lafora disease and MERRF syndrome), Ramsay-Hunt syndrome and late manifesting forms of several other lysosomal storage disorders (GM2 gangliosidosis, Gaucher disease and Niemann-Pick type C disease; see these terms). ## Antenatal diagnosis Prenatal diagnosis is feasible for families in which the disease causing mutation has been identified. ## Genetic counseling Genetic counseling should be proposed. ## Management and treatment Management is supportive only. ## Prognosis ANCLs follow a slowly progressive course with possible survival to the fifth decade. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Adult neuronal ceroid lipofuscinosis

c0022797

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79262

{"gard": ["10973"], "mesh": ["C537950", "D009472"], "omim": ["162350", "204300", "256730", "601780", "610127", "614706", "615362"], "umls": ["C0022797", "C2931675"], "icd-10": ["E75.4"], "synonyms": ["ANCL", "Adult NCL", "Kufs disease"]}

A number sign (#) is used with this entry because this form of peroxisome biogenesis disorder (PBD7B) is caused by homozygous or compound heterozygous mutation in the PEX26 gene (608666) on chromosome 22q11.21. Mutation in PEX26 also causes Zellweger syndrome (PBD7A; 614872). Description The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX26 gene have cells of complementation group 8 (CG8, equivalent to CGA). For information on the history of PBD complementation groups, see 214100. Molecular Genetics Matsumoto et al. (2003) identified homozygosity for a missense mutation (608666.0001) in a patient with neonatal adrenoleukodystrophy (NALD). Matsumoto et al. (2003) identified mutations in the PEX26 gene in patients with NALD (608666.0001) and infantile Refsum disease (IRD) (608666.0005-608666.0007). INHERITANCE \- Autosomal recessive LABORATORY ABNORMALITIES \- Low import of catalase by peroxisomes in patient fibroblasts (import increased or restored by culturing at 30 degrees C) \- Normal but inefficient import of thiolase by peroxisomes in patient fibroblasts (numbers of thiolase-positive peroxisomes increased by culturing at 30 degrees C) MISCELLANEOUS \- Survival to ages 4-12 years \- Based on studies of cell lines MOLECULAR BASIS \- Caused by mutation in the peroxisome biogenesis factor 26 gene (PEX26, 608666.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

PEROXISOME BIOGENESIS DISORDER 7B

c0282527

omim

https://www.omim.org/entry/614873

{"mesh": ["D052919"], "omim": ["614873"], "orphanet": ["772", "44"]}

This article is about the congenital endocrine and muscular disorder. For the vascular condition, see Abdominal aortic aneurysm. Triple A syndrome Other namesAchalasia–addisonianism–alacrima syndrome or Allgrove syndrome[1] MRI of the brain of 12-year-old boy with triple-A syndrome showing hypoplastic lacrimal glands (yellow arrows.) SpecialtyEndocrinology Triple-A syndrome or AAA syndrome, is a rare autosomal recessive congenital disorder. In most cases, there is no family history of it.[2] The syndrome was first identified by Jeremy Allgrove and colleagues in 1978, since then just over 100 cases have been reported.[3] The syndrome involves achalasia, addisonianism (adrenal insufficiency of primary type), and alacrima (insufficiency of tears). Alacrima is usually the earliest manifestation.[4] It is a progressive disorder that can take years to develop the full-blown clinical picture.[5] ## Contents * 1 Presentation * 2 Cause * 3 Diagnosis * 4 Treatment * 5 See also * 6 References * 7 External links ## Presentation[edit] Individuals affected by AAA have adrenal insufficiency/Addison's disease due to ACTH resistance, alacrima (absence of tear secretion), and achalasia (a failure of a ring of muscle fibers, such as a sphincter, to relax) of the lower esophageal sphincter at the cardia which delays food going to the stomach and causes dilation of the thoracic esophagus. There may also be signs of autonomic dysfunction with AAA, such as pupillary abnormalities, an abnormal reaction to intradermal histamine, abnormal sweating, orthostatic hypotension, and disturbances of the heart rate.[6] Hypoglycemia (low blood sugar) is often mentioned as an early sign.[5] The disorder has also been associated with mild mental retardation.[5] The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children.[citation needed] ## Cause[edit] Triple-A syndrome is associated with mutations in the AAAS gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insufficiency Neurologic disorder).[7][8][9] In 2000, Huebner et al. mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster.[10] Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.[4] ALADIN protein is a component of the nuclear pore complex, situated toward its cytoplasmic side. Mutant ALADIN remains mislocalized in the cytoplasm[11] and causes selective failure of nuclear protein import and hypersensitivity to oxidative stress.[12] Mutant ALADIN also causes decreased nuclear import of aprataxin, a repair protein for DNA single-strand breaks, and DNA ligase I.[12] These decreases in DNA repair proteins may allow accumulation of DNA damages that trigger cell death.[citation needed] Nucleoporin ALADIN participates in spindle assembly. ALADIN is employed in specific meiotic stages, including spindle assembly, and spindle positioning.[13] Female mice homozygously null for ALADIN are sterile.[13] ## Diagnosis[edit] Following features of achalasia cardia are seen. On plain x-ray an absence of fundal gas shadow, widened mediastinum and an air fluid level in mediastinum is also seen. The gold standard investigation is a 24 hours manometry of oesophagus. It shows non-relaxation of lower oesophageal sphincter, increased tone of oesophageal sphincter, atonic oesophagus. Bird-beak sign and rat-tail sign can be appreciated on barium swallow.[14][15][16] ## Treatment[edit] There is no definitive cure for this syndrome, because many of the mechanisms implicated have not yet been identified.The only possible treatments address only some of the symptoms. Artificial tear drops are used to remedy the absence of tear secretion, achalasia, if needed, can be treated with surgical intervention and corticosteroids, such as hydrocortisone, are prescribed to solve the surrenal insufficiency.[17] ## See also[edit] * Achalasia * Addisonianism * Alacrima ## References[edit] 1. ^ Online Mendelian Inheritance in Man (OMIM): 231550 2. ^ Dusek, Tina; Korsic, Marta; Koehler, Katrin; Perkovic, Zdravko; Huebner, Angela; Korsic, Mirko (2006). "A Novel AAAS Gene Mutation (p.R194X) in a Patient with Triple A Syndrome". Hormone Research. 65 (4): 171–176. doi:10.1159/000092003. PMID 16543750. S2CID 36128858. 3. ^ M, Gazarian; Ct, Cowell; M, Bonney; Wg, Grigor (January 1995). "The "4A" Syndrome: Adrenocortical Insufficiency Associated With Achalasia, Alacrima, Autonomic and Other Neurological Abnormalities". European Journal of Pediatrics. 154 (1): 18–23. doi:10.1007/BF01972967. PMID 7895750. S2CID 8904441. 4. ^ a b Bharadia, Lalit; Kalla, Mukesh; Sharma, S K; Charan, Rohit; Gupta, J B; Khan, Firoz (2005). "Triple A Syndrome". Indian Journal of Gastroenterology. 24 (5): 217–8. PMID 16361769. 5. ^ a b c Prpic, I.; Huebner, A.; Persic, M.; Handschugg, K.; Pavletic, M. (2003). "Triple A syndrome: genotype-phenotype assessment". Clinical Genetics. 63 (5): 414–417. doi:10.1034/j.1399-0004.2003.00070.x. PMID 12752575. 6. ^ Brooks, B.P.; Kleta, R.; Stuart, C.; Tuchman, M.; Jeong, A.; Stergiopoulos, S.G.; Bei, T.; Bjornson, B.; Russell, L.; Chanoine, J-P.; Tsagarakis, S.; Kalsner, LR.; Stratakis, CA. (2005). "Genotype heterogeneity and clinical phenotype in triple A syndrome". Clinical Genetics. 68 (3): 215–221. doi:10.1111/j.1399-0004.2005.00482.x. PMID 16098009. 7. ^ Huebner, Angela; Kaindl, A.M.; Knobeloch, K.P.; Petzold, H.; Mann, P.; Koehler, K. (2004). "The Triple A Syndrome Is Due to Mutations in Aladin, a Novel Member of the Nuclear Pore Complex". Endocrine Research. 30 (4): 891–899. doi:10.1081/ERC-200044138. PMID 15666842. S2CID 31047487. 8. ^ Salmaggi A, Zirilli L, Pantaleoni C, et al. (2008). "Late-onset triple A syndrome: a risk of overlooked or delayed diagnosis and management". Horm. Res. 70 (6): 364–372. doi:10.1159/000161867. PMID 18953174. S2CID 8097415. 9. ^ "Triple A Syndrome". Genetics Home Reference. February 2010. Retrieved 10 May 2020. 10. ^ Huebner A, Yoon SJ, Ozkinay F, et al. (Nov 2000). "Triple A syndrome--clinical aspects and molecular genetics". Endocr. Res. 26 (4): 751–759. doi:10.3109/07435800009048596. PMID 11196451. S2CID 42579320. 11. ^ M, Krumbholz; K, Koehler; A, Huebner (April 2006). "Cellular Localization of 17 Natural Mutant Variants of ALADIN Protein in Triple A Syndrome - Shedding Light on an Unexpected Splice Mutation". Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire. 84 (2): 243–9. doi:10.1139/o05-198. PMID 16609705. 12. ^ a b Hirano M, Furiya Y, Asai H, Yasui A, Ueno S (February 2006). "ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome". Proc. Natl. Acad. Sci. U.S.A. 103 (7): 2298–303. Bibcode:2006PNAS..103.2298H. doi:10.1073/pnas.0505598103. PMC 1413683. PMID 16467144. 13. ^ a b Carvalhal S, Stevense M, Koehler K, Naumann R, Huebner A, Jessberger R, Griffis ER (September 2017). "ALADIN is required for the production of fertile mouse oocytes". Mol. Biol. Cell. 28 (19): 2470–2478. doi:10.1091/mbc.E16-03-0158. PMC 5597320. PMID 28768824. 14. ^ Wallace, I. R.; Hunter, S. J. (1 August 2012). "AAA syndrome--adrenal insufficiency, alacrima and achalasia". QJM. 105 (8): 803–804. doi:10.1093/qjmed/hcr145. 15. ^ Gaiani, Federica; Gismondi, Pierpacifico; Minelli, Roberta; Casadio, Giovanni; de’Angelis, Nicola; Fornaroli, Fabiola; de’Angelis, Gian Luigi; Manfredi, Marco (29 May 2020). "Case report of a familial triple: a syndrome and review of the literature". Medicine. 99 (22): e20474. doi:10.1097/MD.0000000000020474. 16. ^ Yadav, Prakarti; Kumar, Deepak; Bohra, Gopal K; Garg, Mahendra K (2020). "Triple A syndrome (Allgrove syndrome) – A journey from clinical symptoms to a syndrome". Journal of Family Medicine and Primary Care. 9 (5): 2531. doi:10.4103/jfmpc.jfmpc_237_20. 17. ^ Nicolino, Marc (April 2013). "Triple A syndrome". Orphanet. Retrieved 31 August 2020. ## External links[edit] * Allgrove (AAA) Syndrome at eMedicine * OMIM: 231550 Achalasia Addisonianism Alacrimia syndrome; Triple A syndrome at NIH's Office of Rare Diseases Classification D * ICD-10: E27.4 * OMIM: 231550 * DiseasesDB: 32088 External resources * eMedicine: ped/71 * Orphanet: 869 * v * t * e Nucleus diseases Telomere * Revesz syndrome Nucleolus * Treacher Collins syndrome * Spinocerebellar ataxia 7 * Cajal body: Spinal muscular atrophy Centromere * CENPJ * Seckel syndrome 4 Other * AAAS * Triple-A syndrome * Laminopathy * SMC1A/SMC3 * Cornelia de Lange Syndrome * SETBP1 * Schinzel–Giedion syndrome see also nucleus *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Triple-A syndrome

c0271742

wikipedia

https://en.wikipedia.org/wiki/Triple-A_syndrome

{"gard": ["457"], "mesh": ["C536008"], "icd-10": ["E27.4"], "wikidata": ["Q7843329"]}

A rare headache resulting from a cerebrospinal fluid (CSF) leak with subsequent lowered CSF pressure, characterized clinically by severe headaches which typically worsen upon standing up and get better when lying down. Additional features may include neck stiffness, nausea, vomiting, vertigo, tinnitus, visual disturbances, and cognitive abnormalities, among others, as sagging and displacement of the brain can lead to a variety of lesions and symptoms. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Spontaneous intracranial hypotension

c0751731

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=443180

{"mesh": ["D019585"], "umls": ["C0751731", "C3544264", "C3850067"], "icd-10": ["G96.0"], "synonyms": ["Spontaneous cerebrospinal fluid leak"]}

Pelvic kidney SpecialtyNephrology A pelvic kidney is a normal kidney located in the pelvis, instead of the abdomen. This occurs when a kidney does not ascend from its original location in the pelvis to its final location during fetal development. Typically, the kidney functions normally despite being in the wrong location. Often a person with a pelvic kidney will go through their whole life not even knowing they have this condition, unless it is discovered on newborn kidney ultrasound screening or if complications arise later in life for this or a completely different reason, and during investigations the condition is diagnosed. Pelvic kidneys occur in 1 in every 500 people in the U.S. It is not a harmful condition generally, but can develop complications.[1] ## Causes[edit] In the development of the human embryo, the metanephric kidneys fail to ascend and usually remain at the brim of the pelvis. This clinical scenario may present no signs or symptoms and the kidneys may function normally. It is associated at times with Mullerian dysgenesis. ## Diagnosis[edit] This section is empty. You can help by adding to it. (June 2018) ## References[edit] Wikimedia Commons has media related to Pelvic kidney. 1. ^ Institute for Fetal Health - Fetal pelvic kidney - Children's Memorial Hospital at the Wayback Machine (archived December 1, 2007) * v * t * e Congenital malformations and deformations of urinary system Abdominal Kidney * Renal agenesis/Potter sequence, Papillorenal syndrome * cystic * Polycystic kidney disease * Meckel syndrome * Multicystic dysplastic kidney * Medullary sponge kidney * Horseshoe kidney * Renal ectopia * Nephronophthisis * Supernumerary kidney * Pelvic kidney * Dent's disease * Alport syndrome Ureter * Ectopic ureter * Megaureter * Duplicated ureter Pelvic Bladder * Bladder exstrophy Urethra * Epispadias * Hypospadias * Posterior urethral valves * Penoscrotal transposition Vestigial Urachus * Urachal cyst * Urachal fistula * Urachal sinus This article related to the genitourinary system is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Pelvic kidney

c0221209

wikipedia

https://en.wikipedia.org/wiki/Pelvic_kidney

{"umls": ["C0221209"], "wikidata": ["Q7161802"]}

Spondyloepimetaphyseal dysplasia (SEMD), Pakistani type is characterized by short stature, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints, precocious osteoarthropathy, and normal intelligence. ## Epidemiology The syndrome has been described a large eight-generation consanguineous Pakistani family. ## Clinical description Radiographic features include delayed epiphyseal ossification at the hips and knees, platyspondyly with irregular end plates and narrowed joint spaces, diffuse early osteoarthritic changes (in the spine and hands), mild brachydactyly, and mild metaphyseal abnormalities (predominantly involving the hips and knees). ## Etiology SEMD, Pakistani type is caused by mutations in the PAPSS2 gene (10q22-q24). Mutations in the same gene have been identified in a 14.5-year-old Turkish girl with premature pubarche, hyperandrogenic anovulation, short stature and skeletal dysplasia. ## Genetic counseling SEMD, Pakistani type is inherited in an autosomal recessive manner. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Spondyloepimetaphyseal dysplasia, PAPSS2 type

c2748515

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93282

{"mesh": ["C567551"], "omim": ["612847"], "umls": ["C2748515"], "icd-10": ["Q77.7"], "synonyms": ["Spondyloepimetaphyseal dysplasia, Pakistani type"]}

Undifferentiated carcinoma of liver and intrahepatic biliary tract is an extremely rare epithelial tumor of the liver and biliary tract which presents heterogenous histological findings and not yet fully defined clinicopathological characterisitcs. Patients usually present with nonspecific signs and symptoms, such as abdominal pain, nausea, vomiting, anorexia, weight loss and/or jaundice. Invasive growth, hight metastatic potential and a rapid clinical course are typically associated. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Undifferentiated carcinoma of liver and intrahepatic biliary tract

None

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=424970

{"icd-10": ["C22.0"], "synonyms": ["Undifferentiated carcinoma of liver and IBT"]}

A rare primary immunodeficiency disorder characterized by autosomal dominant inheritance, absolute neutrophil counts below 0.5x10E9/L in the peripheral blood (on three separate occasions over a six month period), granulopoiesis maturation arrest at the promyelocyte/myelocyte stage and early-onset, severe, recurrent bacterial infections. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Autosomal dominant severe congenital neutropenia

c1859966

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=486

{"gard": ["9558"], "mesh": ["C565969"], "omim": ["202700", "257100", "613107", "618752"], "icd-10": ["D70"]}

For general phenotypic information and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy, see 254770. Mapping Greenberg et al. (1987) studied 24 families with JME. Segregation analysis allowed them to reject fully penetrant dominant and recessive models. For the linkage analysis, they assumed a fully penetrant recessive model or a recessive model with 60% penetrance. Using either clinical phenotype or EEG changes to score persons as affected with JME, Greenberg et al. (1987, 1988) found evidence for linkage to BF (138470) and HLA (142800) on chromosome 6p21; the lod score exceeded 3.0 when HLA and BF were used together. Greenberg et al. (1989) and Delgado-Escueta et al. (1989) presented additional evidence for linkage to HLA and BF. Delgado-Escueta et al. (1989) stated in an addendum that linkage with HLA serologic and DNA markers had been confirmed by 2 other groups. In a study of 23 families ascertained through a JME proband, Weissbecker et al. (1991) found evidence for linkage to HLA on 6p (maximum lod score of 3.11 at a male recombination distance of 0.001 and a female recombination distance of 0.2). The results assumed autosomal dominant inheritance with 90% penetrance. Durner et al. (1991) studied 21 families of JME patients and obtained a lod score of 3.9 for linkage to HLA-DQ (146880) assuming a dominant mode of inheritance and 70% penetrance when family members with JME, absence epilepsy, or epilepsy with generalized tonic-clonic seizures were considered affected. The lod score increased to 4.1 when family members with generalized spike-wave discharges on EEG were considered affected. Durner et al. (1991) concluded that a gene locus for several types of generalized idiopathic epilepsy map to 6p. Sander et al. (1995) ascertained 44 families with 452 individuals through patients with either childhood absence epilepsy (ECA1; 600131) or juvenile absence epilepsy (JAE; 607631), both of which are subsets of idiopathic generalized epilepsy. Strong negative lod scores excluded a major susceptibility locus for these disorders in the HLA region on chromosome 6p21. However, suggestive evidence for linkage to HLA was found for a subgroup of 14 families with JME patients (lod score of 1.92 at theta (max) = 0.053) when family members with idiopathic generalized epilepsy or idiopathic generalized tonic-clonic seizures were included as being affected. The authors used a single locus approximation model that assumed either autosomal dominant or recessive inheritance with penetrance of 70%. Sander et al. (1997) reported significant evidence of linkage of JME to a candidate region of 10.1 cM on chromosome 6p21 between the flanking loci HLA-DQ and D6S1019 in a sample of German families. However, JME families they collected elsewhere in the world gave evidence against linkage, suggesting that linkage of JME to HLA may represent a European phenomenon. Greenberg et al. (2000) found evidence of genetic heterogeneity within JME. Their data suggested that JME may be predominantly maternally inherited and that the HLA-linked form is more likely to occur in families of European origin. Molecular Genetics Pal et al. (2003) noted that the critical region of the major JME susceptibility locus that maps to 6p21 is delimited by obligate recombinants at HLA-DQ (146880) and HLA-DP (142858), and that association between JME and a microsatellite marker in the 6p21 region had been reported (Greenberg et al., 2000). They found highly significant linkage disequilibrium (LD) between JME and a core haplotype of 5 SNP and microsatellite markers in this critical region, with LD peaking in the BRD2 gene (601540). In 20 probands from families linked to 6p21, DNA sequencing revealed 2 JME-associated SNP variants in the BRD2 promoter region, but no other potentially causative coding mutations. Pal et al. (2003) suggested that JME at the 6p21 locus may be caused by mutation in the BRD2 gene, a putative nuclear transcriptional regulator and a member of a family of genes that are expressed during development. The authors noted that reported abnormal cerebral microanatomy in JME (Woermann et al., 1999) would be consistent with BRD2 involvement. Nomenclature A locus for juvenile myoclonic epilepsy linked to HLA on chromosome 6p21.3 was originally termed 'EJM1' (Sander et al., 1995). Since then, EJM1 has been used to refer to a different JME phenotype (254770) caused by mutation in the EFHC1 gene (608815) on chromosome 6p12-p11. The locus at 6p21 is symbolized EJM3. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MYOCLONIC EPILEPSY, JUVENILE, SUSCEPTIBILITY TO, 3

c0270853

omim

https://www.omim.org/entry/608816

{"doid": ["0111326"], "mesh": ["D020190"], "omim": ["608816"], "orphanet": ["307"]}

Hutchinson's teeth Other namesHutchinson's incisor, Hutchinson's sign or Hutchinson-Boeck teeth Notched incisors known as Hutchinson's teeth which are characteristic of congenital syphilis Hutchinson's teeth[1] is a sign of congenital syphilis. Affected people have teeth that are smaller and more widely spaced than normal and which have notches on their biting surfaces. It is named after Sir Jonathan Hutchinson, an English surgeon and pathologist, who first described it. Hutchinson's teeth form part of Hutchinson's triad. ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. ## External links[edit] Wikimedia Commons has media related to Hutchinson's teeth. * Hutchinson's teeth at Who Named It? * v * t * e Symptoms and signs relating to infectious diseases Bacterial disease * syphilis * Hutchinson's teeth * Hutchinson's triad * Westphal's sign * Clutton's joints * Dennie–Marfan syndrome Viral disease * measles * Koplik's spots Parasitic disease * African trypanosomiasis * Winterbottom's sign General * Meningism * Fever * Liebermeister's rule * Faget sign * v * t * e Musculoskeletal examination Leg Hip examination * Galeazzi test * Allis test * Barlow maneuver * Ober's test * Ortolani test * Patrick's test * Thomas test * Trendelenburg's sign Knee examination * Ballottement * Clarke's test * Drawer test * Lachman test * Patellar tap * Pivot-shift test * Valgus stress test * meniscus * Apley grind test * McMurray test * ligament and meniscus * Unhappy triad Foot and ankle * Hubscher's maneuver * Mulder's sign * Simmonds' test * Thompson test * Ankle * Simmonds' test General * Straight leg raise * Lasègue's sign * Gait abnormality * Trendelenburg gait * Unequal leg length Arm Shoulder examination * Apprehension test * Jobe's test * Neer impingement sign * Yergason's test * rotator cuff * Hawkins–Kennedy test * Watson's test Elbow examination * Cozen's test * Elbow extension test Hand and wrist * Durkan's test * Finkelstein's test * Froment's sign * Lunotriquetral shear test * Phalen maneuver * Tinel sign * Watson's test Spine * Gaenslen's test * Low back pain * Waddell's signs * Lower back flexibility * Schober's test * sacroiliitis * Larrey's sign Other * Range of motion * Palpation * Codman triangle This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Hutchinson's teeth

c0020186

wikipedia

https://en.wikipedia.org/wiki/Hutchinson%27s_teeth

{"gard": ["8160"], "mesh": ["D013590"], "umls": ["C0020186"], "wikidata": ["Q1424702"]}

Jacobsen syndrome is a condition caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder. The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including the development of speech and motor skills (such as sitting, standing, and walking). Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention-deficit/hyperactivity disorder (ADHD). Jacobsen syndrome is also associated with an increased likelihood of autism spectrum disorders, which are characterized by impaired communication and socialization skills. Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance. More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cells that are necessary for blood clotting. Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood. ## Frequency The estimated incidence of Jacobsen syndrome is 1 in 100,000 newborns. More than 200 affected individuals have been reported. ## Causes Jacobsen syndrome is caused by a deletion of genetic material at the end of the long (q) arm of chromosome 11. The size of the deletion varies among affected individuals, with most affected people missing 5 million to 16 million DNA building blocks (also written as 5 Mb to 16 Mb). In almost all affected people, the deletion includes the tip of chromosome 11. Larger deletions tend to cause more severe signs and symptoms than smaller deletions. The features of Jacobsen syndrome are likely related to the loss of multiple genes on chromosome 11. Depending on its size, the deleted region can contain from about 170 to more than 340 genes. Many of these genes have not been well characterized. However, genes in this region appear to be critical for the normal development of many parts of the body, including the brain, facial features, and heart. Only a few genes have been studied as possible contributors to the specific features of Jacobsen syndrome; researchers are working to determine which additional genes may be associated with this condition. ### Learn more about the gene and chromosome associated with Jacobsen syndrome * FLI1 * chromosome 11 Additional Information from NCBI Gene: * ARHGAP32 * ETS1 ## Inheritance Pattern Most cases of Jacobsen syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, although they can pass the chromosome deletion to their children. Between 5 and 10 percent of people with Jacobsen syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which a segment from chromosome 11 has traded places with a segment from another chromosome. In a balanced translocation, no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with some missing genetic material and some extra genetic material. Individuals with Jacobsen syndrome who inherit an unbalanced translocation are missing genetic material from the end of the long arm of chromosome 11 and have extra genetic material from another chromosome. These chromosomal changes result in the health problems characteristic of this disorder. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Jacobsen syndrome

c0795841

medlineplus

https://medlineplus.gov/genetics/condition/jacobsen-syndrome/

{"gard": ["307"], "mesh": ["D054868"], "omim": ["147791"], "synonyms": []}

A rare mixed neuronal-glial tumor characterized by a supratentorial space-occupying lesion in periventricular location, often with prominent cystic change. The histological hallmark of this low-grade neoplasm is its pseudopapillary appearance with a single layer of cuboidal cells around hyalinized blood vessels, associated with sheets or focal collections of neuronal cells. Clinical presentation is variable and non-specific, most frequently with headache and seizures. Prognosis is favorable after complete resection. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Papillary glioneuronal tumor

c2985174

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251962

{"umls": ["C2985174"], "synonyms": ["PGNT", "Pseudopapillary ganglioglioneurocytoma", "Pseudopapillary neurocytoma with glial differentiation"]}

A number sign (#) is used with this entry because of evidence that infantile liver failure syndrome-2 (ILFS2) is caused by homozygous or compound heterozygous mutation in the NBAS gene (608025) on chromosome 2p24. Description Infantile liver failure syndrome-2 is an autosomal recessive disorder characterized by recurrent episodes of acute liver failure during intercurrent febrile illness. Patients first present in infancy or early childhood, and there is complete recovery between episodes with conservative treatment (summary by Haack et al., 2015). For a discussion of genetic heterogeneity of infantile liver failure syndrome, see ILFS1 (615438). Clinical Features In 10 unrelated families, most apparently of European descent, Haack et al. (2015) identified 11 patients, aged 3 to 37 years, with onset of recurrent acute liver failure in infancy. Most patients had onset in the first 2 years of life, although 1 had the first episode at age 6 years. Episodic liver failure in these patients was precipitated by intercurrent febrile illness, and liver function recovered completely with conservative management in the interval. Crises were manifest by vomiting, lethargy, increased liver enzymes, jaundice, and coagulopathy. Some patients developed secondary hyperammonemia, hypoglycemia, or encephalopathy. Four patients had comorbid features, such as cardiomyopathy, autoimmune gastrointestinal disease, and epilepsy, but none of these features were present in more than 1 patient. None of the 11 patients died, but 2 had older sibs who died of acute liver failure in early infancy. Inheritance The transmission pattern of ILFS2 in the families reported by Haack et al. (2015) was consistent with autosomal recessive inheritance. Molecular Genetics In 5 unrelated German patients with ILFS2, Haack et al. (2015) identified homozygous or compound heterozygous mutations in the NBAS gene (see, e.g., 608025.0002-608025.0006). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the families with available data. Screening of the NBAS gene in 15 additional unrelated patients with acute liver failure identified biallelic NBAS mutations in 6 patients from 5 families. All 11 affected individuals carried at least 1 missense mutation on 1 allele. Seven of the mutations were predicted to result in a loss of function, and all remaining missense mutations or in-frame deletions were clustered in 2 regions in the first half of the gene: exons 8 to 12 encoding the quinoprotein amine dehydrogenase beta-chain-like domain, and exons 21 to 28 encoding the secretory pathway sec39 domain. Patient fibroblasts showed a reduction of NBAS levels to 18 to 36% of control values, indicating a substantial impairment of protein translation and/or stability. Patient fibroblasts showed normal glycosylation patterns but an increase in expression of genes involved in the ER stress response compared to controls. Haack et al. (2015) suggested that a catabolic state with high energy demands during febrile infections may cause derailment of ER/Golgi vesicular transport. INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Liver failure, acute, episodic Gastrointestinal \- Vomiting during episodes SKIN, NAILS, & HAIR Skin \- Jaundice during episodes NEUROLOGIC Central Nervous System \- Lethargy during episodes METABOLIC FEATURES \- Hypoglycemia during episodes HEMATOLOGY \- Coagulopathy during episodes LABORATORY ABNORMALITIES \- Elevated liver enzymes during episodes \- Hyperammonemia during episodes MISCELLANEOUS \- Onset in the first years of life \- Recurrent episodes of liver failure during intercurrent infections \- Complete recovery during intervals MOLECULAR BASIS \- Caused by mutation in the neuroblastoma-amplified sequence gene (NBAS, 608025.0002 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

INFANTILE LIVER FAILURE SYNDROME 2

c3809651

omim

https://www.omim.org/entry/616483

{"omim": ["616483"], "orphanet": ["464724"], "synonyms": []}

This article may be too technical for most readers to understand. Please help improve it to make it understandable to non-experts, without removing the technical details. (September 2015) (Learn how and when to remove this template message) TRIANGLE disease Other namesTPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion disease TRIANGLE disease has an autosomal recessive pattern of inheritance TRIANGLE disease is a rare genetic disorder of the immune system. TRIANGLE stands for “TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion” where TPP2 is the causative gene. This disease manifests as recurrent infection, autoimmunity, and neurodevelopmental delay. TRIANGLE disease was first described in a collaborative study by Dr. Helen C. Su[1] from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Dr. Sophie Hambleton[2] from the University of Newcastle and their collaborators in 2014.[3] The disease was also described by the group of Ehl et al.[4] ## Contents * 1 Genetics * 1.1 Inheritance * 2 Diagnosis * 2.1 Clinical manifestations * 2.2 Laboratory manifestations * 3 Treatment * 4 References * 5 External links ## Genetics[edit] TRIANGLE disease is caused by loss-of-function mutations in the gene TPP2, which stands for tripeptidyl peptidase II. TPP2 maps to human chromosome 13q32-q33, has 32 exons, and encodes for a 1249 amino acid protein.[5][6] The genetic model for this disease is loss-of-function. This means that for people with TRIANGLE disease, the gene TPP2 is unable to produce protein or produce functional protein.[citation needed] Functionally, TPPII has a key role in recycling amino acids, which are protein building blocks, a fundamental cellular process. Although the body can use alternative amino acid recycling pathways to compensate for loss of TPPII, the up-regulation of alternative pathways can cause new cellular abnormalities in itself with subsequent effects on glycolysis, adaptive immunity, and innate immunity. Consequently, individuals without functioning TPPII have severe disease.[3] ### Inheritance[edit] TRIANGLE disease is inherited in an autosomal recessive manner. In autosomal recessive inheritance, two copies of an abnormal gene must be present in order for the disease to develop. Typically, this means both parents of an affected child silently carry one abnormal gene. This also means this also explains why reported cases of TRIANGLE disease have involved consanguinity or geographically isolated communities.[citation needed] Parents of a child with TRIANGLE disease have a 25% chance of having another affected child with each pregnancy. This risk is independent of prior children’s status. For example, if the first two children in a family are affected, the next child has the same 25% risk of inheriting the mutation. All affected individuals have two abnormal copies of TPP2. Children who inherit only one abnormal copy of TPP2 will not develop TRIANGLE disease although they may have affected children, particularly if they marry within the family.[citation needed] ## Diagnosis[edit] ### Clinical manifestations[edit] Two family pedigrees of TPPII deficiency patients. Clinically, TRIANGLE disease is characterized combined immunodeficiency, severe autoimmunity, and developmental delay. Patients typically present in early childhood with recurrent bacterial and viral infections of the middle ear and respiratory tract. Additionally, patients develop severe, difficult to treat autoimmunity. This autoimmunity includes auto-antibody mediated destruction of red blood cells, neutrophils, and platelets; central nervous system lupus erythematous with stroke; and hepatitis. Patients also have mild to moderate developmental delay.[3][4] ### Laboratory manifestations[edit] The clinical symptoms are caused by abnormalities of the immune system and disruption of basic cellular functions. Patients show markedly decreased circulating T cells, B cells and natural killer (NK) cells, with severely reduced naive T cells and hypergammaglobulinemia.[3] ## Treatment[edit] Once a diagnosis is made, the treatment is based on an individual’s clinical condition and may include standard management for autoimmunity and immunodeficiency. Hematopoietic stem cell transplantation has cured the immune abnormalities in one TRIANGLE patient, although the neurodevelopmental delay would likely remain. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.[7] ## References[edit] 1. ^ Dr. Helen C. Su www.niaid.nih.gov, retrieved 26 September 2015 2. ^ Dr. Sophie Hambleton www.ncl.ac.uk, retrieved 26 September 2015 3. ^ a b c d Lu, W.; Zhang, Y.; McDonald, D.; Jing, H.; Carroll, B.; Robertson, N.; Zhang, Q.; Griffin, H.; Sanderson, S.; Lakey, J.; Morgan, N.; Reynard, L.; Zheng, L.; Murdock, H.; Turvey, S.; Hackett, S.; Prestidge, T.; Hall, J.; Cant, A.; Matthews, H.; Santibanez Koref, M.; Simon, A.; Korolchuk, V.; Lenardo, M.; Hambleton, S.; Su, H. (2014). "Dual Proteolytic Pathways Govern Glycolysis and Immune Competence" (PDF). Cell. 159 (7): 1578–1590. doi:10.1016/j.cell.2014.12.001. PMC 4297473. PMID 25525876. 4. ^ a b Stepensky, P.; Rensing-Ehl, A.; Gather, R.; Revel-Vilk, S.; Fischer, U.; Nabhani, S.; Beier, F.; Brummendorf, T. H.; Fuchs, S.; Zenke, S.; Firat, E.; Pessach, V. M.; Borkhardt, A.; Rakhmanov, M.; Keller, B.; Warnatz, K.; Eibel, H.; Niedermann, G.; Elpeleg, O.; Ehl, S. (20 November 2014). "Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency". Blood. 125 (5): 753–761. doi:10.1182/blood-2014-08-593202. PMC 4463807. PMID 25414442. 5. ^ McKusick, Victor. "#190470 TRIPEPTIDYL PEPTIDASE II; TPP2". OMIM. Johns Hopkins University. Retrieved 10 July 2015. 6. ^ "TPP2 Gene". GeneCards. Weizmann Institute of Science. Retrieved 10 July 2015. 7. ^ Clinicaltrials.gov, study ID: NCT00246857, NCT00001467, and others ## External links[edit] Classification D * ICD-10: D61.0 External resources * Orphanet: 444463 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

TRIANGLE disease

None

wikipedia

https://en.wikipedia.org/wiki/TRIANGLE_disease

{"orphanet": ["444463"], "synonyms": ["Evans syndrome associated with primary immunodeficiency", "TPPII deficiency", "TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion disease", "TRIANGLE disease", "Tripeptidyl-peptidase II deficiency"], "wikidata": ["Q24975604"]}

A number sign (#) is used with this entry because of evidence that Leber congenital amaurosis with early-onset deafness (LCAEOD) is caused by heterozygous mutation in the TUBB4B gene (602660) on chromosome 9q34. Description Leber congenital amaurosis with early-onset deafness is an autosomal dominant syndrome manifesting as early-onset and severe photoreceptor and cochlear cell loss. Some patients show extinguished responses on electroretinography and moderate to severe hearing loss at birth (Luscan et al., 2017). Clinical Features Luscan et al. (2017) studied 4 families in which 5 affected individuals exhibited early-onset retinal degeneration and hearing loss. Diagnosis of eye disease occurred by age 3 years, with 3 of the 5 patients showing no responses on electroretinography (ERG) at birth. Funduscopy showed features of advanced retinitis pigmentosa in a 34-year-old affected French woman (family 1), who had marked reduction in caliber of retinal vessels, generalized choroid atrophy, marked macular rearrangement, and numerous peripheral pigmentary deposits. Her 5.5-year-old affected son showed similar abnormalities, although to a much lesser extent. Hearing loss in the 5 patients was diagnosed within the first decade of life, and ranged from mild to severe. Vocal audiograms of the affected mother and son from family 1 were consistent with pure-tone traces, suggesting endocochlear deafness. The maternal grandmother from family 1, who developed hearing loss in her fourth decade and reported no vision problems, had retinal degeneration on fundus examination and optical coherence tomography, but photopic and scotopic ERGs were normal. All patients had normal neurologic and psychomotor development, and brain MRI was normal in an affected Danish boy (family 4) at age 2 months. The authors designated the severe and early-onset retinal degeneration seen in these patients to be consistent with advanced Leber congenital amaurosis type 2 (see LCA2, 204100), although they noted that all 5 had high hypermetropia, which was atypical for LCA2. Molecular Genetics By whole-exome sequencing in 3 affected members of a family (family 1) with early-onset retinal degeneration and hearing loss, Luscan et al. (2017) identified heterozygosity for a missense mutation in the TUBB4B gene (R391H; 602660.0001) in the affected mother and son. The maternal grandmother, who had milder symptoms, was found to be mosaic for the mutation, which was present in 29% of reads and had arisen de novo. Analysis of an in-house whole-exome sequencing database identified 3 more probands with LCAEOD and mutations in TUBB4B, 2 with the same R391H mutation, and 1 with an R391C substitution (602660.0002). In 2 of the families, the mutation was shown to have arisen de novo, but in the third family (family 2), the mutation was inherited from an unaffected mosaic father, in whom the variant was present in only 13% of reads. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Sensorineural hearing loss, early-onset \- Endocochlear deafness Eyes \- Retinal degeneration, early-onset \- Reduced visual acuity \- High hypermetropia \- Retinal vessel attenuation \- Generalized choroid atrophy \- Macular rearrangements \- Peripheral pigmentary deposits \- Severely reduced to extinguished responses on electroretinography MISCELLANEOUS \- Symptoms occur within the first decade of life \- Onset at birth in some patients MOLECULAR BASIS \- Caused by mutation in the beta-4B tubulin gene (TUBB4B, 602660.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

LEBER CONGENITAL AMAUROSIS WITH EARLY-ONSET DEAFNESS

c4693498

omim

https://www.omim.org/entry/617879

{"omim": ["617879"]}

Silver syndrome belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and, frequently, development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. Both types involve the lower limbs; the complex types may also involve the upper limbs, although to a lesser degree. In addition, the complex types may affect the brain and parts of the nervous system involved in muscle movement and sensations. Silver syndrome is a complex hereditary spastic paraplegia. The first sign of Silver syndrome is usually weakness in the muscles of the hands. These muscles waste away (amyotrophy), resulting in abnormal positioning of the thumbs and difficulty using the fingers and hands for tasks such as handwriting. People with Silver syndrome often have high-arched feet (pes cavus) and spasticity in the legs. The signs and symptoms of Silver syndrome typically begin in late childhood but can start anytime from early childhood to late adulthood. The muscle problems associated with Silver syndrome slowly worsen with age, but affected individuals can remain active throughout life. ## Frequency Although Silver syndrome appears to be a rare condition, its exact prevalence is unknown. ## Causes Mutations in the BSCL2 gene cause Silver syndrome. The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. The BSCL2 gene is active (expressed) in cells throughout the body, particularly in nerve cells that control muscle movement (motor neurons) and in brain cells. Within cells, seipin is found in the membrane of a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. BSCL2 gene mutations that cause Silver syndrome likely lead to an alteration in the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness and spasticity. In Silver syndrome, only specific motor neurons are involved, resulting in the hand and leg muscles being solely affected. Some people with Silver syndrome do not have an identified mutation in the BSCL2 gene. The cause of the condition in these individuals is unknown. ### Learn more about the gene associated with Silver syndrome * BSCL2 ## Inheritance Pattern Silver syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, the affected person inherits the mutation from one affected parent. However, some people who inherit the altered gene never develop features of Silver syndrome. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not. Rarely, Silver syndrome is caused by new mutations in the gene and occurs in people with no history of the disorder in their family. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Silver syndrome

c2931276

medlineplus

https://medlineplus.gov/genetics/condition/silver-syndrome/

{"gard": ["4219"], "mesh": ["C536644"], "omim": ["270685"], "synonyms": []}

Bethlem myopathy Bethlem myopathy has an autosomal dominant pattern of inheritance (autosomal recessive form exists as well[1]) Bethlem myopathy is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a mutation in one of the three genes coding for type VI collagen.[2] These include COL6A1, COL6A2, and COL6A3.[3] Gower's sign, tiptoe-walking and contractures of the joints (especially the fingers) are typical signs and symptoms of the disease. Bethlem myopathy could be diagnosed based on clinical examinations and laboratory tests may be recommended. Currently there is no cure for the disease and symptomatic treatment is used to relieve symptoms and improve quality of life. Bethlem myopathy affects about 1 in 200,000 people.[4] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 3 Treatment * 4 Epidemiology * 5 References * 6 External links ## Signs and symptoms[edit] The onset of this disease can begin even before birth but is more commonly in childhood or later into adult life. The progression is slow, with symptoms of weakness and walking difficulties sometimes not presenting until middle age. Early symptoms include Gower's sign ("climbing" up the thighs with the hands when rising from the floor) and tiptoe-walking caused by the beginning of contractures. Contractures of the fingers are a typical symptom of Bethlem myopathy but not of the related Ullrich's myopathy (which does include contractures of arms and legs, as does Bethlem myopathy). Serum creatine kinase is elevated in Bethlem myopathy, as there is ongoing muscle cell death. Patients with Bethlem myopathy may expect a normal life span and continued mobility into adulthood. ## Diagnosis[edit] The disease could be diagnosed based on a clinical examination, which identifies signs and symptoms generally associated with the people who have the condition. Additional laboratory tests may be recommended. Creatine kinase (CK) blood test results will generally be normal or only slightly elevated. Skin biopsy, MRI of the muscles, electromyography (EMG) are the main testing methods of the disease. The diagnosis can be confirmed with genetic testing of the COL6A1, COL6A2, and COL6A3 genes.[5] Phenotypes of overlap between Ullrich congenital muscular dystrophy (UCMD) and Bethlem can be assumed. In the differential diagnosis of UCDM, even in patients without finger contractures, Bethlem myopathy could be considered.[6] ## Treatment[edit] Currently there is no cure for the disease. Symptomatic treatment, which aims to relieve symptoms and improve quality of life is the main treatment method of Bethlem myopathy. It is believed that physical therapy, stretching exercises, orthoses such as braces and splints, and mobility aids like a walker or wheelchair are beneficial to patient's condition.[5] Surgical options could be considered in rare instances, in order to help with joint contractures or scoliosis.[5] Contractures of the legs can be alleviated with heel-cord surgery followed by bracing and regular physical therapy. Repeated surgeries to lengthen the heel cords may be needed as the child grows to adulthood.[2] ## Epidemiology[edit] According to a Japanese study from 2007 Bethlem myopathy affects about 1 in 200,000 people.[4] A 2009 study concerning the prevalence of genetic muscle disease in Northern England estimated the prevalence of Bethlem myopathy to be at 0.77:100,000.[7] Together with the UCMD it is believed to be underdiagnosed. Both conditions have been described in individuals from a variety of ethnic backgrounds.[8] ## References[edit] 1. ^ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Bethlem myopathy". www.orpha.net. Retrieved 23 December 2017. 2. ^ a b Jobsis GJ, Boers JM, Barth PG, de Visser M (1999). "Bethlem myopathy: a slowly-progressive congenital muscular dystrophy with contractures". Brain. 122 (4): 649–655. doi:10.1093/brain/122.4.649. PMID 10219778. 3. ^ Lampe AK, Bushby KM (September 2005). "Collagen VI related muscle disorders" (PDF). J. Med. Genet. 42 (9): 673–85. doi:10.1136/jmg.2002.002311. PMC 1736127. PMID 16141002. 4. ^ a b Okada M et al (2007) Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan. Neurolog 69:1035–1042 5. ^ a b c "Bethlem myopathy | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-10-19. 6. ^ Reed, Umbertina Conti; Ferreira, Lucio Gobbo; Liu, Enna Cristina; Resende, Maria Bernadete Dutra; Carvalho, Mary Souza; Marie, Suely Kazue; Scaff, Milberto (September 2005). "Ullrich congenital muscular dystrophy and bethlem myopathy: clinical and genetic heterogeneity". Arquivos de Neuro-Psiquiatria. 63 (3B): 785–790. doi:10.1590/S0004-282X2005000500013. ISSN 0004-282X. 7. ^ Norwood, Fiona L. M.; Harling, Chris; Chinnery, Patrick F.; Eagle, Michelle; Bushby, Kate; Straub, Volker (2009). "Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population". Brain: A Journal of Neurology. 132 (Pt 11): 3175–3186. doi:10.1093/brain/awp236. ISSN 1460-2156. PMC 4038491. PMID 19767415. 8. ^ Lampe, Anne Katrin; Flanigan, Kevin M.; Bushby, Katharine Mary; Hicks, Debbie (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Collagen Type VI-Related Disorders", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID 20301676, retrieved 2020-10-19 ## External links[edit] Classification D * ICD-10: G71.2 * OMIM: 158810 * MeSH: C535436 * DiseasesDB: 32019 External resources * Orphanet: 610 * Image at wustl.edu * v * t * e Diseases of muscle, neuromuscular junction, and neuromuscular disease Neuromuscular- junction disease * autoimmune * Myasthenia gravis * Lambert–Eaton myasthenic syndrome * Neuromyotonia Myopathy Muscular dystrophy (DAPC) AD * Limb-girdle muscular dystrophy 1 * Oculopharyngeal * Facioscapulohumeral * Myotonic * Distal (most) AR * Calpainopathy * Limb-girdle muscular dystrophy 2 * Congenital * Fukuyama * Ullrich * Walker–Warburg XR * dystrophin * Becker's * Duchenne * Emery–Dreifuss Other structural * collagen disease * Bethlem myopathy * PTP disease * X-linked MTM * adaptor protein disease * BIN1-linked centronuclear myopathy * cytoskeleton disease * Nemaline myopathy * Zaspopathy Channelopathy Myotonia * Myotonia congenita * Thomsen disease * Neuromyotonia/Isaacs syndrome * Paramyotonia congenita Periodic paralysis * Hypokalemic * Thyrotoxic * Hyperkalemic Other * Central core disease Mitochondrial myopathy * MELAS * MERRF * KSS * PEO General * Inflammatory myopathy * Congenital myopathy * v * t * e Diseases of collagen, laminin and other scleroproteins Collagen disease COL1: * Osteogenesis imperfecta * Ehlers–Danlos syndrome, types 1, 2, 7 COL2: * Hypochondrogenesis * Achondrogenesis type 2 * Stickler syndrome * Marshall syndrome * Spondyloepiphyseal dysplasia congenita * Spondyloepimetaphyseal dysplasia, Strudwick type * Kniest dysplasia (see also C2/11) COL3: * Ehlers–Danlos syndrome, types 3 & 4 * Sack–Barabas syndrome COL4: * Alport syndrome COL5: * Ehlers–Danlos syndrome, types 1 & 2 COL6: * Bethlem myopathy * Ullrich congenital muscular dystrophy COL7: * Epidermolysis bullosa dystrophica * Recessive dystrophic epidermolysis bullosa * Bart syndrome * Transient bullous dermolysis of the newborn COL8: * Fuchs' dystrophy 1 COL9: * Multiple epiphyseal dysplasia 2, 3, 6 COL10: * Schmid metaphyseal chondrodysplasia COL11: * Weissenbacher–Zweymüller syndrome * Otospondylomegaepiphyseal dysplasia (see also C2/11) COL17: * Bullous pemphigoid COL18: * Knobloch syndrome Laminin * Junctional epidermolysis bullosa * Laryngoonychocutaneous syndrome Other * Congenital stromal corneal dystrophy * Raine syndrome * Urbach–Wiethe disease * TECTA * DFNA8/12, DFNB21 see also fibrous proteins *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Bethlem myopathy

c1834674

wikipedia

https://en.wikipedia.org/wiki/Bethlem_myopathy

{"gard": ["873"], "mesh": ["C535436"], "umls": ["CN029274"], "orphanet": ["610"], "wikidata": ["Q831363"]}

A number sign (#) is used with this entry because of evidence that neurodevelopmental disorder with spasticity and poor growth (NEDSG) is caused by homozygous mutation in the UFC1 gene (610554) on chromosome 1q23. Clinical Features Nahorski et al. (2018) reported 8 patients with a severe neurodevelopmental disorder apparent soon after birth or in early infancy. The age of the patients ranged from almost 3 to 5 years, except for 2 sisters originally reported by Anazi et al. (2017) who were 16 and 23 years of age. The patients presented with axial hypotonia, delayed psychomotor development, poor feeding, and failure to thrive. They developed peripheral spasticity with hyperreflexia and were unable to walk, sit, speak, or grasp. They had poor overall growth, and most had microcephaly. Additional variable features included contractures, nonspecific facial dysmorphisms, and ocular movement abnormalities. Three patients had seizures, which were intractable in 2 patients. Brain imaging was normal in some patients, but showed delayed myelination and/or white matter changes in other patients. Inheritance The transmission pattern of NEDSG in the families reported by Nahorski et al. (2018) was consistent with autosomal recessive inheritance. Molecular Genetics In affected members of 3 consanguineous Saudi families with NEDSG, Nahorski et al. (2018) identified a homozygous missense mutation in the UFC1 gene (T106I; 610554.0001). An unrelated Swiss boy with NEDSG was found to have a different homozygous mutation in the UFC1 gene (R23Q; 610554.0002). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. In vitro functional expression studies showed that both mutations caused impaired thioester binding with UFM1 (610553). Patient cells also showed decreased UFC1 intermediate formation with UFM1. The decrease in function was consistent with a hypomorphic allele, and Nahorski et al. (2018) suggested that complete loss of function would be embryonic lethal. The findings suggested that impaired posttranslational protein ufmylation results in neurodevelopmental defects. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Other \- Failure to thrive \- Poor growth HEAD & NECK Head \- Microcephaly Face \- Dysmorphic facial features, variable (in some patients) Eyes \- Eye movement abnormalities \- Poor fixation \- Oculomotor apraxia ABDOMEN Gastrointestinal \- Poor feeding \- Gastric reflux \- Constipation SKELETAL \- Contractures MUSCLE, SOFT TISSUES \- Axial hypotonia NEUROLOGIC Central Nervous System \- Delayed psychomotor development, profound \- Intellectual disability \- Inability to sit or walk \- Poor or absent speech \- Poor head control \- Spasticity \- Hyperreflexia \- Clonus \- Intention tremor \- Seizures (in some patients) \- White matter abnormalities (in some patients) \- Delayed myelination (in some patients) MOLECULAR BASIS \- Caused by mutation in the ubiquitin-fold modifier-conjugating enzyme 1 gene (UFC1, 610554.0001 )/ ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

NEURODEVELOPMENTAL DISORDER WITH SPASTICITY AND POOR GROWTH

None

omim

https://www.omim.org/entry/618076

{"omim": ["618076"]}

A rare genetic primary bone dysplasia disease characterized by progressive osteosclerosis and platyspondyly. ## Epidemiology Less than 30 cases of Dysosteosclerosis have been reported in the literature to date. ## Clinical description The disease is characterized by sclerosis of the skull base, ribs, clavicles, scapulae, mid-diaphyses and increased bone fragility. Patients have a prominent forehead, narrow midface, flattening of the vertebral bodies and dental anomalies. Short stature, optic atrophy, hearing impairment, epilepsy, skin changes, and progressive psychomotor deficit are frequent. ## Etiology The disease is caused by mutations in SLC29A3. This gene encodes a nucleoside transporter. Mutations in this gene may also cause Faisalabad histiocytosis, Rosai-Dorfman disease, H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome. Parental consanguinity has been noted in some cases. Mutations in osteopetrosis genes TNFRSF11A and TCIRG1 can also cause dysosteosclerosis. ## Diagnostic methods Sequencing combined by deletion and duplication analysis is possible. ## Differential diagnosis Osteopetrosis is more common than dysosteosclerosis and distinguishing features are the presence of sclerotic platyspondyly as well as widened and relatively radiolucent sub-metaphyseal regions of long tubular bones with sclerotic diaphysis. Responsible genes include OSTM1, SNX10, CA2, TCIRG1, TNFSF11, CLCN7, PLEKHM1, TNFRSF11A, and LRP5. In Pyle disease, there is important metaphyseal expansion with cortical thinning of the tubular bones well into the diaphyses. There can be mild platyspondyly and skull sclerosis but not as much as in dysosteoscleoris. Genu valgum is a key clinical feature. The responsible gene is SFRP4. In BANDDOS (Brain abnormalities, neurodegeneration, and dysosteosclerosis), there are bone changes similar to dysoseosclerosis, osteopetrosis or Pyle disease, but there is also neurological disease of neonatal, childhood or adult onset. The responsible gene is CSF1R. ## Genetic counseling Dysosteosclerosis is inherited in an autosomal recessive manner for SLC29A3, TNFRSF11A and TCIRG1 mutation. An X-linked pedigree has also been reported. ## Management and treatment Management is mostly supportive, bone marrow transplantation was tried in one individual without success. ## Prognosis The overall prognosis is generally poor, although, as in osteopetrosis, there is a wide spectrum of severity. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Dysosteosclerosis

c0432262

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1782

{"gard": ["2012"], "mesh": ["C562973"], "omim": ["224300"], "umls": ["C0432262"], "icd-10": ["Q78.8"]}

A form of cutaneous lupus erythematosus (CLE) that can present either as a non-scarring, annular photo-distributed dermatosis or psoriasiform plaques. This disorder is associated with anti-Ro/SSA antibodies and can be drug-induced. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Subacute cutaneous lupus erythematosus

c0024140

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163525

{"mesh": ["D008178"], "umls": ["C0024140"], "icd-10": ["L93.1"]}

A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by epiphyseal and vertebral dysplasia and abnormalities of the external ears (severe microtia or anotia) and the nose (hypoplastic nose with bifid tip, triangular nares, or anteverted nares). Additional variable findings include short stature, localized aplasia cutis, hypodontia, synophrys, agenesis of the corpus callosum, and cardiac, gastrointestinal, and/or urogenital malformations, among others. Psychomotor development may be delayed. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

EVEN-plus syndrome

c4225180

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=496751

{"omim": ["616854"], "synonyms": ["Epiphysial-vertebral-ear dysplasia-nose-plus associated findings syndrome"]}

This article does not cite any sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Gastrointestinal neuroectodermal tumor" – news · newspapers · books · scholar · JSTOR (November 2018) (Learn how and when to remove this template message) Gastrointestinal Neuroectodermal Tumor (GNET) GNET. Tumor cells with prominent nucleoli and clear cytoplasm are arranged in well-defined nests surrounded by dense fibrous stroma with admixed giant cells. A gastrointestinal neuroectodermal tumor is a neuroectodermal tumor that appears in the gastrointestinal system. ## References[edit] ## External links[edit] Classification D * ICD-O: 9044/3 * MeSH: D018227 This oncology article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Gastrointestinal neuroectodermal tumor

None

wikipedia

https://en.wikipedia.org/wiki/Gastrointestinal_neuroectodermal_tumor

{"wikidata": ["Q5526840"]}

The infection rate of HIV/AIDS in Ivory Coast is estimated at 2.70% in adults ages 15–49.[1] Ivory Coast has a generalized HIV epidemic with the highest prevalence rate in the West African region. The prevalence rate appears to have remained relatively stable for the past decade, with recent declines among pregnant women in urban areas. Civil conflict in the country continues to hinder the collection of new national HIV-related data. In 2005, a national AIDS Indicator Survey was completed, which provided accurate data on various aspects of the epidemic, including prevalence rates among diverse demographic sub-groups. Populations at comparatively high risk for HIV infection include women ages 20–24, people in prostitution, youth and the military. The prolonged political-military crisis, in addition to exacerbating the vulnerability of these groups, is likely to have created additional at-risk populations given the large-scale military deployment, massive population displacement, and increase in poverty.[2] Political instability, delays in the disarmament process and the threat of armed insurgency continue to be major challenges and barriers to external assistance. The prolonged sociopolitical crisis has disrupted and restricted access to health and other public services, while at the same time increasing HIV transmission and vulnerability among many sub-populations. Ivory Coast has a more developed public health and education system in terms of human resources and infrastructure than many of its neighbors, but the overall health system is weak, and health and economic gains have been reversed by the crisis.[2] Blood screening services and treatment for sexually transmitted infections and tuberculosis are very limited. Regions in the North and West, which have not been under government control, have experienced a complete and prolonged disruption of public-sector services and an exodus of skilled professionals. Major disparities exist between urban and rural health services, with a paucity of health professionals and private practitioners outside the major cities.[2] ## See also[edit] * Health in Ivory Coast * HIV/AIDS in Africa ## References[edit] 1. ^ "Côte d'Ivoire 2016 Country factsheet". UNAIDS. Retrieved 9 January 2018. 2. ^ a b c "2008 Country Profile: Cote d'Ivoire". U.S. Department of State (2008). This article incorporates text from this source, which is in the public domain. * v * t * e HIV/AIDS in Africa By location * Angola * Benin * Botswana * Democratic Republic of the Congo * Côte d'Ivoire (Ivory Coast) * Egypt * Ethiopia * Ghana * Guinea * Kenya * Lesotho * Libya * Madagascar * Malawi * Mali * Mozambique * Namibia * Nigeria * Rwanda * Senegal * South Africa * Swaziland * Tanzania * Uganda * Zambia * Zimbabwe African AIDS activists * Zackie Achmat * Gideon Byamugisha * Nkosi Johnson * Noerine Kaleeba * Didier Lestrade * Philly Lutaaya * Nelson Mandela * Elizabeth Mataka * Ntare Mwine * Joel Gustave Nana Ngongang * Simon Nkoli * Agnes Nyamayarwo * Joseph Sonnabend * Sheila Tlou * v * t * e HIV/AIDS topics HIV/AIDS HIV * HIV * Lentivirus * structure and genome * subtypes * CDC classification * disease progression rates * HIV/AIDS * diagnosis * management * pathophysiology * prevention * research * vaccination * PrEP * WHO disease staging system for HIV infection and disease * Children * Teens / Adults * Countries by AIDS prevalence rate Conditions * Signs and symptoms * AIDS-defining clinical condition * Diffuse infiltrative lymphocytosis syndrome * Lipodystrophy * Nephropathy * Neurocognitive disorders * Pruritus * Superinfection * Tuberculosis co-infection * HIV Drug Resistance Database * Innate resistance to HIV * Serostatus * HIV-positive people * Nutrition * Pregnancy History * History * Epidemiology * Multiple sex partners * Timeline * AIDS Museum * Timothy Ray Brown * Women and HIV/AIDS Social * AIDS orphan * Catholic Church and HIV/AIDS * Circumcision and HIV * Criminal transmission * Discrimination against people * Economic impact * Cost of treatment * HIV-affected community * HIV/AIDS activism * HIV/AIDS denialism * Red ribbon * Safe sex * Sex education * List of HIV-positive people * People With AIDS Self-Empowerment Movement * HIV/AIDS in the porn industry Culture * Discredited HIV/AIDS origins theories * International AIDS Conference * International AIDS Society * Joint United Nations Programme on HIV/AIDS (UNAIDS) * Media portrayal of HIV/AIDS * Misconceptions about HIV/AIDS * President's Emergency Plan for AIDS Relief (PEPFAR) * The SING Campaign * Solidays * Treatment Action Campaign * World AIDS Day * YAA/Youthforce * "Free Me" * Larry Kramer * Gay Men's Health Crisis * ACT UP * Silence=Death Project HIV/AIDS pandemic by region / country Africa * Angola * Benin * Botswana * Democratic Republic of the Congo * Egypt * Eswatini * Ethiopia * Ghana * Guinea * Côte d'Ivoire (Ivory Coast) * Kenya * Lesotho * Madagascar * Malawi * Mali * Mozambique * Namibia * Niger * Nigeria * Rwanda * Senegal * Tanzania * South Africa * Uganda * Zambia * Zimbabwe North America * Canada * Mexico * El Salvador * Guatemala * Honduras * Nicaragua United States * New York City Caribbean * Haiti * Jamaica * Dominican Republic South America * Bolivia * Brazil * Colombia * Guyana * Peru Asia * Afghanistan * Armenia * Azerbaijan * Bahrain * Bangladesh * Bhutan * Cambodia * China (PRC) (Yunnan) * East Timor * India * Indonesia * Iran * Iraq * Japan * Jordan * North Korea * Laos * Malaysia * Myanmar (Burma) * Nepal * Pakistan * Philippines * Saudi Arabia * Sri Lanka * Taiwan (ROC) * Thailand * United Arab Emirates * Turkey * Vietnam Europe * United Kingdom * Russia * Ukraine Oceania * Australia * New Zealand * Papua New Guinea * List of countries by HIV/AIDS adult prevalence rate * List of HIV/AIDS cases and deaths registered by region *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

HIV/AIDS in Ivory Coast

None

wikipedia

https://en.wikipedia.org/wiki/HIV/AIDS_in_Ivory_Coast

{"wikidata": ["Q2881775"]}

Ménière disease is a disorder of the inner ear that affects balance and hearing. This condition is characterized by sudden episodes of extreme dizziness (vertigo), a roaring sound in the ears (tinnitus), a feeling of pressure or fullness in the ears, and fluctuations in hearing. Episodes are often associated with nausea and vomiting, and they can severely disrupt activities of daily living. The episodes associated with Ménière disease generally last several hours. Studies suggest that episodes can be triggered by stress, tiredness (fatigue), emotional upset, illness, and dietary factors. The timing of these episodes is unpredictable; affected individuals may experience a cluster of episodes within a short period, followed by months or years without any symptoms. Ménière disease usually appears in adulthood, most often in a person's 40s or 50s. It is much less common in children and young adults. The symptoms of the disorder typically begin in one ear, although they may later involve both ears. Some people with Ménière disease have no symptoms of the disorder between episodes, particularly in the early stages of the disease. Over time, however, many affected individuals develop ongoing problems with unsteadiness, tinnitus, and a feeling of fullness in the ears. Additionally, permanent hearing loss eventually develops in many people with this disorder. ## Frequency The prevalence of Ménière disease varies in different geographic regions and ethnic groups. It appears to be more common in people of European descent than in those with other backgrounds. In the United States, there are an estimated 615,000 people with Ménière disease, and more than 45,000 new cases are diagnosed each year. ## Causes The cause of Ménière disease is unknown, although it probably results from a combination of environmental and genetic factors. Ménière disease is thought to be related to abnormalities of the inner ear, which contains structures that are needed for normal hearing and balance. Episodes of vertigo, tinnitus, and hearing loss likely result from fluctuating amounts of fluid in the inner ear. These changes disrupt signals sent from the inner ear to the brain that are related to sound and the body's position and movement. Researchers have studied many possible risk factors for Ménière disease, including viral infections, trauma to the inner ear, noise pollution, allergies, abnormal immune system responses, and migraines. Studies have also examined changes in more than a dozen genes that might contribute to the signs and symptoms of this condition. However, none of the factors studied so far appears to play a major role in Ménière disease. Researchers are looking for additional environmental and genetic factors that are associated with this complex disorder. ## Inheritance Pattern Most cases of Ménière disease are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families. When the disorder is familial, it most often has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to increase the risk of the disorder. However, no associated genes have been identified. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Ménière disease

c0025281

medlineplus

https://medlineplus.gov/genetics/condition/meniere-disease/

{"gard": ["10340"], "mesh": ["D008575"], "omim": ["156000"], "synonyms": []}

Congenital discontinuity of the oesophagus Esophageal atresia Other namesOesophageal atresia Common anatomical types of esophageal atresia a) Esophageal atresia with distal tracheoesophageal fistula (86%), Gross C. b) Isolated esophageal atresia without tracheoesophageal fistula (7%), Gross A. c) H-type tracheoesophageal fistula (4%), Gross E.[1] SpecialtyPediatrics Esophageal atresia is a congenital medical condition (birth defect) that affects the alimentary tract. It causes the esophagus to end in a blind-ended pouch rather than connecting normally to the stomach. It comprises a variety of congenital anatomic defects that are caused by an abnormal embryological development of the esophagus. It is characterized anatomically by a congenital obstruction of the esophagus with interruption of the continuity of the esophageal wall.[clarification needed] ## Contents * 1 Signs and symptoms * 1.1 Complications * 1.2 Associated birth defects * 2 Diagnosis * 2.1 Classification * 3 Treatment * 3.1 Treatment options * 3.2 Treatment complications * 3.3 Other related complications * 4 Epidemiology * 5 References * 6 Further reading * 7 External links ## Signs and symptoms[edit] Plain X-ray of the chest and abdomen showing a feeding tube unable to move beyond an upper esophageal pouch. Plain x-ray with contrast in the upper esophagus above the atresia. Surgical treatment of the condition. Schematic representation. This birth defect arises in the fourth fetal week, when the trachea and esophagus should begin to separate from each other. It can be associated with disorders of the tracheoesophageal septum.[2] ### Complications[edit] Any attempt at feeding could cause aspiration pneumonia as the milk collects in the blind pouch and overflows into the trachea and lungs. Furthermore, a fistula between the lower esophagus and trachea may allow stomach acid to flow into the lungs and cause damage. Because of these dangers, the condition must be treated as soon as possible after birth.[citation needed] ### Associated birth defects[edit] Other birth defects may co-exist, particularly in the heart, but sometimes also in the anus, spinal column, or kidneys. This is known as VACTERL association because of the involvement of Vertebral column, Anorectal, Cardiac, Tracheal, Esophageal, Renal, and Limbs. It is associated with polyhydramnios in the third trimester.[citation needed] ## Diagnosis[edit] This condition may be visible, after about 26 weeks, on an ultrasound. On antenatal USG, the finding of an absent or small stomach in the setting of polyhydramnios was considered a potential symptom of esophageal atresia. However, these findings have a low positive predictive value. The upper neck pouch sign is another sign that helps in the antenatal diagnosis of esophageal atresia and it may be detected soon after birth as the affected infant will be unable to swallow its own saliva.[citation needed] On plain X-ray, a feeding tube will not be seen pass through the esophagus and remain coiled in the upper oesophageal pouch.[3] ### Classification[edit] This condition takes several different forms, often involving one or more fistulas connecting the trachea to the esophagus (tracheoesophageal fistula). Gross[4] Vogt[5] Ladd[6] Name(s) Description Frequency[1] \- Type 1 \- Esophageal Agenesis Very rare complete absence of the esophagus, not included in classification by Gross or Ladd N/A Type A Type 2 I "Long Gap", “Pure” or “Isolated” Esophageal Atresia Characterized by the presence of a “gap” between the two esophageal blind pouches with no fistula present. 7% Type B Type 3A II Esophageal Atresia with proximal TEF (tracheoesophageal fistula) The upper esophageal pouch connects abnormally to the trachea. The lower esophageal pouch ends blindly. 2-3% Type C Type 3B III, IV Esophageal Atresia with distal TEF (tracheoesophageal fistula) The lower esophageal pouch connects abnormally to the trachea. The upper esophageal pouch ends blindly. 86% Type D Type 3C V Esophageal Atresia with both proximal and distal TEFs (two tracheoesophageal fistulas) Both the upper and lower esophageal pouch make an abnormal connection with the trachea in two separate, isolated places. <1% Type E Type 4 \- TEF (tracheoesophageal fistula) ONLY with no Esophageal Atresia, H-Type Esophagus fully intact and capable of its normal functions, however, there is an abnormal connection between the esophagus and the trachea. Not included in classification by Ladd 4% ## Treatment[edit] ### Treatment options[edit] Treatments for the condition vary depending on its severity. The most immediate and effective treatment in the majority of cases is a surgical repair to close the fistula/s and reconnect the two ends of the esophagus to each other. Although this is usually done through an incision between the ribs on right side of the baby, a technique using three small incisions (thoracoscopy) is being used at some centers.[citation needed] In a minority of cases, the gap between upper and lower esophageal segments may be too long to bridge. In these situations traditional surgical approaches include gastrostomy followed by gastric pull-up, colonic transposition and jejunum transposition.[7] Gastric pull-up has been the preferred approach at many specialized centers, including Great Ormond Street (London) and Mott Children's Hospital (Ann Arbor).[8] Gastrostomy, or G-tube, allows for tube feedings into the stomach through the abdominal wall. Often a cervical esophagostomy will also be done, to allow the saliva which is swallowed to drain out a hole in the neck. Months or years later, the esophagus may be repaired, sometimes by using a segment of bowel brought up into the chest, interposing between the upper and lower segments of esophagus.[citation needed] In some of these so-called long gap cases, though, an advanced surgical treatment developed by John Foker, MD,[9] may be utilized to elongate and then join together the short esophageal segments. Using the Foker technique, surgeons place traction sutures in the tiny esophageal ends and increase the tension on these sutures daily until the ends are close enough to be sewn together. The result is a normally functioning esophagus, virtually indistinguishable from one congenitally well formed. Unfortunately, the results have been somewhat difficult to replicate by other surgeons and the need for multiple operations has tempered enthusiasm for this approach. The optimal treatment in cases of long gap esophageal atresia remains controversial.[10] Magnetic compression method is another method for repairing long-gap esophageal atresia. This method does not require replacing the missing section with grafts of the intestine or other body parts. Using electromagnetic force to attract the upper and lower ends of the esophagus together was first tried in the 1970s by using steel pellets attracted to each other by applying external electromagnets to the patient. In the 2000s a further refinement was developed by Mario Zaritzky's group and others. The newer method uses permanent magnets and a balloon. 1. The magnets are inserted into the upper pouch via the baby's mouth or nose, and the lower via the gastrotomy feeding tube hole (which would have had to be made anyway to feed the baby, therefore not requiring any additional surgery). 2. The distance between the magnets is controlled by a balloon in the upper pouch, between the end of the pouch and the magnet. This also controls the force between the magnets so it is not strong enough to cause damage. 3. After the ends of the esophagus have stretched enough to touch, the upper magnet is replaced by one without a balloon and the stronger magnetic attraction causes the ends to fuse (anastomosis).[11][12][13][14] In April 2015 Annalise Dapo became the first patient in the United States to have their esophageal atresia corrected using magnets.[11][15] ### Treatment complications[edit] Post operative complications may include a leak at the site of closure of the esophagus. Sometimes a stricture, or tight spot, will develop in the esophagus, making it difficult to swallow. Esophageal stricture can usually be dilated using medical instruments. In later life, most children with this disorder will have some trouble with either swallowing or heartburn or both. Esophageal dismotility occurs in 75-100% of patients. After esophageal repair (anastomosis) the relative flaccidity of former proximal pouch (blind pouch, above) along with esophageal dysmotility can cause fluid buildup during feeding. Owing to proximity, pouch ballooning can cause tracheal occlusion. Severe hypoxia ("dying spells") follows and medical intervention can often be required. ### Other related complications[edit] Tracheomalacia a softening of the trachea, usually above the carina (carina of trachea), but sometimes extensive in the lower bronchial tree as well—is another possible serious complication. A variety of treatments for tracheomalacia associated with esophageal atresia are available. If not severe, the condition can be managed expectantly since the trachea will usually stiffen as the infant matures into the first year of life. When only the trachea above the carina is compromised, one of the "simplest" interventions is aortopexy wherein the aortic loop is attached to the rear of the sternum, thereby mechanically relieving pressure from the softened trachea. An even simpler intervention is stenting. However, epithelial cell proliferation and potential incorporation of the stent into the trachea can make subsequent removal dangerous.[citation needed] The incidence of asthma, bronchitis, bronchial hyperresponsiveness, and recurrent infections in adolescent and adult esophageal atresia survivors far exceeds that of their healthy peers.[16] During the first decade of surgical repair of EA, as much as 20% of patients succumbed to pneumonia. From there on, pneumonia has remained as a major pulmonary complication and a reason for readmissions after repair of EA.[16][17] The risk factors of pneumonia within the first five years of life include other acute respiratory infections and high number of esophageal dilatations.[18] ## Epidemiology[edit] It occurs in approximately 1 in 3000 live births.[1] Congenital esophageal atresia (EA) represents a failure of the esophagus to develop as a continuous passage. Instead, it ends as a blind pouch. Tracheoesophageal fistula (TEF) represents an abnormal opening between the trachea and esophagus. EA and TEF can occur separately or together. EA and TEF are diagnosed in the ICU at birth and treated immediately.[citation needed] The presence of EA is suspected in an infant with excessive salivation (drooling) and in a newborn with drooling that is frequently accompanied by choking, coughing and sneezing. When fed, these infants swallow normally but begin to cough and struggle as the fluid returns through the nose and mouth. The infant may become cyanotic (turn bluish due to lack of oxygen) and may stop breathing as the overflow of fluid from the blind pouch is aspirated (sucked into) the trachea. The cyanosis is a result of laryngospasm (a protective mechanism that the body has to prevent aspiration into the trachea). Over time respiratory distress will develop.[citation needed] If any of the above signs/symptoms are noticed, a catheter is gently passed into the esophagus to check for resistance. If resistance is noted, other studies will be done to confirm the diagnosis. A catheter can be inserted and will show up as white on a regular x-ray film to demonstrate the blind pouch ending. Sometimes a small amount of barium (chalk-like liquid) is placed through the mouth to diagnose the problems.[citation needed] Treatment of EA and TEF is surgery to repair the defect. If EA or TEF is suspected, all oral feedings are stopped and intravenous fluids are started. The infant will be positioned to help drain secretions and decrease the likelihood of aspiration. Babies with EA may sometimes have other problems. Studies will be done to look at the heart, spine and kidneys.Surgery to repair EA is essential as the baby will not be able to feed and is highly likely to develop pneumonia. Once the baby is in condition for surgery, an incision is made on the side of the chest. The esophagus can usually be sewn together. Following surgery, the baby may be hospitalized for a variable length of time. Care for each infant is individualized.Its very commonly seen in a newborn with imperforate anus.[citation needed] ## References[edit] 1. ^ a b c Spitz L (May 2007). "Oesophageal atresia". Orphanet Journal of Rare Diseases. 2: 24. doi:10.1186/1750-1172-2-24. PMC 1884133. PMID 17498283. 2. ^ Clark DC (February 1999). "Esophageal atresia and tracheoesophageal fistula". American Family Physician. 59 (4): 910–6, 919–20. PMID 10068713. 3. ^ Higano NS, Bates AJ, Tkach JA, Fleck RJ, Lim FY, Woods JC, Kingma PS (February 2018). "Pre- and post-operative visualization of neonatal esophageal atresia/tracheoesophageal fistula via magnetic resonance imaging". Journal of Pediatric Surgery Case Reports. 29: 5–8. doi:10.1016/j.epsc.2017.10.001. PMC 5794017. PMID 29399473. 4. ^ Gross RE (1953). The Surgery of Infancy and Childhood. Philadelphia: WB Saunders. 5. ^ Vogt EC (November 1929). "Congenital esophageal atresia". American Journal of Roentgenology. 22: 463–465. 6. ^ Ladd WE (1944). "The surgical treatment of esophageal atresia and tracheoesophageal fistulas". The New England Journal of Medicine. 230 (21): 625–637. doi:10.1056/nejm194405252302101. 7. ^ "Esophageal Atresia Treatment Program". Children’s Hospital Boston. Archived from the original on 4 June 2011. Retrieved 1 June 2012. 8. ^ Hirschl RB, Yardeni D, Oldham K, Sherman N, Siplovich L, Gross E, et al. (October 2002). "Gastric transposition for esophageal replacement in children: experience with 41 consecutive cases with special emphasis on esophageal atresia". Annals of Surgery. 236 (4): 531–9, discussion 539-41. doi:10.1097/00000658-200210000-00016. PMC 1422608. PMID 12368682. 9. ^ "Esophageal atresia - symptoms, tests, Foker treatment". Children’s Hospital Boston. Archived from the original on 11 July 2012. Retrieved 1 June 2012. 10. ^ Kunisaki SM, Foker JE (June 2012). "Surgical advances in the fetus and neonate: esophageal atresia". Clinics in Perinatology. 39 (2): 349–61. doi:10.1016/j.clp.2012.04.007. PMID 22682384. 11. ^ a b Mims B (10 April 2015). "Pioneering WakeMed procedure corrects infant's rare disorder". WRAL.com. Raleigh-Durham: Capitol Broadcasting. 12. ^ "Dr Zaritzky Pioneers Non-surgical Option for Babies with Esophageal Atresia". Department of Radiology. University of Chicago. 13 April 2015. Archived from the original on 14 April 2015. 13. ^ Oehlerking A, Meredith JD, Smith IC, Nadeau PM, Gomez T, Trimble ZA, Mooney DP, Trumper DL (June 2011). "A hydraulically controlled nonoperative magnetic treatment for long gap esophageal atresia" (PDF). Transactions of the ASME-W-Journal of Medical Devices. 5 (2): 027511. doi:10.1115/1.3589828. Archived from the original (PDF) on 2015-04-02. 14. ^ Lovvorn III HN, Baron CM, Danko ME, Novotny NM, Bucher BT, Johnston KK, Zaritzky MF (2014). "Staged repair of esophageal atresia: Pouch approximation and catheter-based magnetic anastomosis". Journal of Pediatric Surgery Case Reports. 2 (4): 170–175. doi:10.1016/j.epsc.2014.03.004. 15. ^ "New, non-invasive procedure for infant at WakeMed is first of its kind in U.S." WTVD-TV. Raleigh-Durham. 10 April 2015. 16. ^ a b Sistonen S, Malmberg P, Malmström K, Haahtela T, Sarna S, Rintala RJ, Pakarinen MP (November 2010). "Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults". The European Respiratory Journal. 36 (5): 1106–12. doi:10.1183/09031936.00153209. PMID 20351029. 17. ^ Louhimo I, Lindahl H (1983). "Esophageal atresia: primary results of 500 consecutively treated patients". J Pediatr Surg. 18 (3): 217–229. doi:10.1016/s0022-3468(83)80089-x. PMID 6875767. 18. ^ Nurminen P, Koivusalo A, Hukkinen M, Pakarinen M (December 2019). "Pneumonia after Repair of Esophageal Atresia-Incidence and Main Risk Factors". European Journal of Pediatric Surgery. 29 (6): 504–509. doi:10.1055/s-0038-1675775. hdl:10138/300624. PMID 30469161. ## Further reading[edit] * Harmon CM, Coran AG (1998). "Congenital Anomalies of the Esophagus". Pediatric Surgery (5th ed.). St Louis, KY: Elsevier Science Health Science Division. ISBN 0-8151-6518-8. ## External links[edit] * GenReview/NIH/UW entry on Esophageal Atresia/Tracheoesophageal Fistula Overview Classification D * ICD-10: Q39.0, Q39.1 * ICD-9-CM: 750.3 * MeSH: D004933 * DiseasesDB: 30035 External resources * MedlinePlus: 000961 * eMedicine: ped/2934 radio/704 * Orphanet: 1199 * v * t * e Congenital malformations and deformations of digestive system Upper GI tract Tongue, mouth and pharynx * Cleft lip and palate * Van der Woude syndrome * tongue * Ankyloglossia * Macroglossia * Hypoglossia Esophagus * EA/TEF * Esophageal atresia: types A, B, C, and D * Tracheoesophageal fistula: types B, C, D and E * esophageal rings * Esophageal web (upper) * Schatzki ring (lower) Stomach * Pyloric stenosis * Hiatus hernia Lower GI tract Intestines * Intestinal atresia * Duodenal atresia * Meckel's diverticulum * Hirschsprung's disease * Intestinal malrotation * Dolichocolon * Enteric duplication cyst Rectum/anal canal * Imperforate anus * Rectovestibular fistula * Persistent cloaca * Rectal atresia Accessory Pancreas * Annular pancreas * Accessory pancreas * Johanson–Blizzard syndrome * Pancreas divisum Bile duct * Choledochal cysts * Caroli disease * Biliary atresia Liver * Alagille syndrome * Polycystic liver disease *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Esophageal atresia

c0014850

wikipedia

https://en.wikipedia.org/wiki/Esophageal_atresia

{"gard": ["6381"], "mesh": ["D004933"], "umls": ["C0014850"], "icd-9": ["750.3"], "orphanet": ["1199"], "wikidata": ["Q298233"]}

For a phenotypic description and a discussion of genetic heterogeneity of androgenetic alopecia, see AGA1 (109200). Mapping Ellis et al. (2001) compared allele frequencies of 3 androgen receptor gene (AR; 313700) polymorphisms, a StuI restriction fragment length polymorphism (RFLP) and 2 triplet repeat polymorphisms, in cases with cosmetically significant baldness (54 young and 392 older men) and controls (107 older men) with no indication of baldness. The StuI restriction site was found in all but 1 (98.1%) of the 54 young bald men (p = 0.0005) and in 92.3% of older balding men (p = 0.000004) but in only 76.6% of nonbald men. The combination of shorter CAG (polyglutamine) and GGC (polyglycine) triplet repeat lengths was also more prevalent in bald men (p = 0.03). The ubiquity of the StuI restriction site and higher incidence of shorter triplet repeat haplotypes in bald men suggested that these markers are very close to a functional variant that is a necessary component of the polygenic determination of male pattern baldness. Functional mutation in or near the AR gene may explain the reported high levels of expression of this gene in the balding scalp. Hillmer et al. (2005) demonstrated that genetic variation in the AR gene is the cardinal prerequisite for the development of early-onset androgenetic alopecia, with an etiologic fraction of 0.46. The investigation of a large number of genetic variants covering the AR locus suggested that a polyglycine-encoding GGN repeat in exon 1 is a plausible candidate for conferring the functional effect. The X-chromosomal location of the androgen receptor gene stressed the importance of the maternal line in the inheritance of AGA. The findings were presumably consistent with the notion that women are bald only if homozygous. The findings were not consistent, however, with the resemblance of fathers and sons with respect to androgenetic alopecia (Kuster and Happle, 1984; Ellis et al., 1998), since sons always inherit the X chromosome from their mothers. Ellis et al. (2007) analyzed approximately 1,200 fathers and sons from 703 Caucasian Australian families, of whom 78% and 30%, respectively, were affected with AGA to some degree, and found that whereas the SNP rs6152 was strongly associated with baldness (p less than 0.0001), the CAG and GGN repeat polymorphisms were not. The authors suggested that the causative variant was likely in the noncoding region, and yet to be identified. In a genomewide association study for androgenetic alopecia involving a total of 1,437 men with alopecia and 1,338 male controls, Richards et al. (2008) found significant association at chromosome 20p11 (see AGA3, 612421) and confirmed the importance of the AR gene in androgenetic alopecia. They found that 14% of men harbored at least 1 risk allele at both 20p11.22 and the AR gene, and that this was associated with a markedly increased risk of androgenetic alopecia (odds ratio, 7.12; p = 3.7 x 10(-15) in their Swiss cohort). *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

ALOPECIA, ANDROGENETIC, 2

c2678038

omim

https://www.omim.org/entry/300710

{"mesh": ["C567473"], "omim": ["300710"]}

endocrinological condition Euthyroid sick syndrome Other namesSick euthyroid syndrome (SES); thyroid allostasis in critical illness, tumours, uremia and starvation (TACITUS); nonthyroidal illness syndrome (NTIS); low T3 low T4 syndrome SpecialtyEndocrinology Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control[1] wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness. The classical phenotype of this condition is often seen in starvation, critical illness, or patients in the intensive care unit. Similar endocrine phenotypes are observed in fetal life and in hibernating mammals.[2] The most common hormone pattern in nonthyroidal illness syndrome is low total and free T3, elevated rT3, and normal T4 and TSH levels, although T4 and TSH suppression may occur in more severe or chronic illness.[3] This classical pattern results from type 1 allostatic load, i.e. a stress response resulting from lacking energy, oxygen, and glutathione.[2] An alternative phenotype with a largely inverse hormonal pattern is seen in several physiological and pathological conditions, including pregnancy, obesity, endurance training, and psychiatric diseases. It is typically associated with high-T3 syndrome, increased plasma protein binding of thyroid hormones, and an elevated set point of the homeostatic system. It represents a response to type-2 allostatic load.[2] ## Contents * 1 Classical phenotype (type 1 thyroid allostasis) * 1.1 Causes * 1.2 Pathophysiology * 1.2.1 Deiodinases * 1.2.2 Hypothalamic-pituitary-thyroid axis downregulation * 1.2.3 Cytokines * 1.2.4 Thyroid hormone receptors * 1.2.5 Thyroid hormone transporters * 1.2.6 Binding proteins * 1.2.7 Drugs * 1.3 Fasting * 2 Alternative phenotype (type 2 thyroid allostasis) * 3 Conditions with mixed phenotypes * 3.1 Psychiatry * 3.2 Exercise * 3.3 Environmental conditions * 4 Diagnosis * 5 Treatment * 6 History * 7 See also * 8 References * 9 Further reading * 10 External links ## Classical phenotype (type 1 thyroid allostasis)[edit] ### Causes[edit] Causes of classical euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, anorexia nervosa, sepsis, trauma,[4] cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, kidney failure, cirrhosis, diabetic ketoacidosis,[1] surgery, infection, brain injury, shock, cancer,[5] and HIV.[6] Outside the hospital setting, euthyroid sick syndrome (nonthyroidal illness syndrome - NTIS) has been assumed closely related with a series of chronic diseases, such as inflammatory bowel disease,[7] chronic fatigue syndrome,[8] and autoimmune diseases.[5] Additionally, an NTIS-like phenotype can be present in major depressive disorder,[5] as well as overexercise.[2] ### Pathophysiology[edit] In critical illness, the activity of different deiodinases is altered. Humoral and neuronal inputs at the level of the hypothalamus may adjust the set point of thyroid homeostasis. This may play an important role in the pathogenesis of the central component of thyroid allostasis in critical illness, tumors, uremia and starvation (TACITUS).[9] In addition, both illness and medication (e.g. salicylates and heparin) may impair plasma protein binding of thyroid hormones, resulting in reduced levels of total hormones, while free hormone concentrations may be temporarily elevated. Euthyroid sick syndrome probably represents an overlap of an allostatic response with pathologic reactions and drug interferences.[2] Allostatic overload may result in wasting syndrome and myxedema coma. Thyroid storm, though, represents allostatic failure, where the organism is unable to develop NTIS in the situation of thyrotoxicosis.[2] #### Deiodinases[edit] D1, D2, and D3 regulate the levels of T4, T3, and rT3. Three primary deiodinases are responsible for thyroid hormone conversion and breakdown. Type 1 (D1) deiodinates T4 to the biologically active T3, as well as the hormonally inactive and possibly inhibitory rT3.[3][5] Type 2 (D2) converts T4 into T3, and breaks down rT3. D3 produces rT3 from T4, and breaks down T3. The balance of D2 and D3 is important for overall T3/rT3 balance.[5][10] In NTIS, the concentrations of these deiodinases are altered, although whether NTIS is the cause or effect of this in peripheral tissues is unclear; in some studies, the alterations in thyroid hormone concentrations occurred before the changes in deiodinase activity.[5] Typically, peripheral D1 and D2 are downregulated, while peripheral D3 is upregulated; this is associated with lower T4 and increased rT3.[3][5] #### Hypothalamic-pituitary-thyroid axis downregulation[edit] Thyrotropin releasing hormone (TRH) neurons in the hypothalamus integrate global signals about the body's energy state. They may be stimulated by signals such as leptin, alpha-MSH, and catecholamines; and inhibited by glucocorticoids, neuropeptide Y, and agouti-related peptide.[2] The HPT Axis. In critical illness, inflammation increases tanycyte D2 in the paraventricular nucleus (PVN) of the hypothalamus, leading to local tissue hyperthyroidism. There may also be decreased central D3.[3][5] This causes negative feedback on the HPT axis, and therefore reduced TRH gene expression in the PVN. This is exemplified by the common NTIS phenotype of low TSH even in the face of peripheral hypothyroidism.[3][5][10][2] #### Cytokines[edit] Illness can cause inflammation, which often involves an increase in cytokines such as TNFa, IL-1, and IL-6. Cytokines are implicated in NTIS.[10][3] IL-1β has been shown to decrease liver D1,[10] as well as thyroid hormone receptor (THR) levels. IL-6 and TNFa downregulate D1 and suppress TSH, are negatively correlated with fT3, and are positively correlated with rT3.[3] NF-κB also inhibits D1, and decreases the expression of Thyroid receptors α and β.[3] IFNy inhibits thyroid and Tg release, and also inhibits the upregulation of TSH receptors.[11] #### Thyroid hormone receptors[edit] In chronic liver and renal (kidney) failure, increased THR expression occurs. In contrast, in acute illness such as sepsis and trauma, decreased THR expression occurs.[5] #### Thyroid hormone transporters[edit] During NTIS, alterations arise in the concentrations of thyroid hormone transporters such as MCT8 and MCT10, although whether the levels are increased or decreased depends on the study. The altered concentrations are thought to be a result of NTIS, rather than a cause; a study in rabbits showed that administering thyroid hormones normalized transporter expression.[5] #### Binding proteins[edit] Decreased thyroxine-binding globulin (TBG) occurs following bypass surgery, and in chronic illness, a less effective form of TBG with lower affinity for thyroxine is synthesized. Reduced quantities of bound thyroid result, leading to decreased total thyroid measurements. Decreases in total thyroid may be more severe than alternations in free hormone levels.[5] #### Drugs[edit] Dopamine and corticosteroids, commonly given in the hospital setting, can suppress TSH and suppress conversion of T4 to T3.[3][5] Other drugs such as estrogen, contraceptives, salicylates, and phenytoin can alter the binding of TBG to TH, resulting in different TH concentrations.[3] Additionally, lithium disrupts thyroid function,[2] and thyromimetic endocrine disrupters may downregulate the HPT axis.[2] ### Fasting[edit] Fasting is a common response in inflammation and critical illness. Originally, selenium deficiency as a result of malnutrition was thought to reduce D1 catalytic activity, but this theory has not been supported as a cause of NTIS.[3][5] A fasting response is common in critical illness. NTIS as a result of fasting may be regarded as a healthy and adaptive mechanism that reduces energy expenditure.[10] Fasting in healthy, euthyroid people causes reduced T3 and elevated rT3, although TSH is usually unchanged.[3][5][10] Even moderate weight loss can lower T3.[2] This may be primarily via reduced levels of leptin (the satisfaction hormone). Low leptin levels can downregulate hypothalamic TRH neurons and cause a reduction in TSH.[5][10] Ιn fasting animals, administering leptin reverses NTIS symptoms and restores thyroid hormone concentrations.[5] In obesity, increased leptin increases TSH and T3, and lowers rT3, possibly as an attempt to increase energy expenditure and return to weight set point.[2] Other signals associated with hunger also affect the HPT axis. Insulin and bile acids, which are elevated after a meal, lead to increased D2 activity,[2] therefore increasing T3 and reducing rT3. Low leptin increases NPY and AGRP (associated with appetite), which inhibit TRH gene expression; this effect is enhanced by ghrelin (the hunger hormone).[5] a-MSH stimulates TRH gene expression in the PVN. This is enhanced by leptin, and inhibited by low leptin. a-MSH is also antagonized by AGRP.[5] ## Alternative phenotype (type 2 thyroid allostasis)[edit] An anti-NTIS phenotype is observed in some circumstances, wherein TSH, T3, and T4 are generally elevated rather than suppressed. This can occur during pregnancy, obesity, cold adaptation, stay in high altitudes, endurance exercise, acute psychosis, and post-traumatic stress disorder.[2][12] According to newer theories,[2] elevated concentrations of TSH and thyroid hormones in type 2 allostasis result from an up-regulated set point of the feedback loop, which ensues from increased TRH expression in the basolateral amygdala and the paraventricular nucleus of the hypothalamus in response to stress.[13][14] High-T3 syndrome in thyroid carcinoma may result from autonomous thyroid hormone secretion or overexpression of type 2 deiodinase in cancer cells rather than from type 2 allostasis.[15][16][17][18] ## Conditions with mixed phenotypes[edit] ### Psychiatry[edit] Stress suppresses TSH,[5] and alterations in thyroid hormone levels may arise in psychiatric illness. In major depressive disorder, an NTIS-like phenotype may be observed, with reduced T3 and increased rT3. T4 may be elevated, and TSH is usually normal, although TSH's normal circadian rhythm may be disrupted.[2] Bipolar 1 and PTSD can exemplify an anti-NTIS phenotype, with upregulation of the HPT axis and increased T3. This may also occur during acute schizophrenic episodes.[2] ### Exercise[edit] After exercise, a transient increase occurs in TSH, T4, and T3, but this is thought to be due to increased blood concentration as a result of dehydration.[2] The effects normalize after rest. After long-term heavy strain, levels of thyroid hormones decrease.[2] This is exacerbated by other stressors such as undernutrition and lack of sleep, such as in a military training setting. During endurance exercise, before exhaustion, elevated thyroid hormone levels may happen due to increased expected energy demand (type 2 allostatic load).[2] ### Environmental conditions[edit] Cold exposure and stay at high altitude may lead to type 1 or type 2 phenotype, depending on duration and other boundary conditions (which determine whether or not stress is associated with energy deprivation).[12][19] ## Diagnosis[edit] Affected patients may have normal, low, or slightly elevated TSH depending on the spectrum and phase of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 levels are generally increased, while FT3 is decreased. FT4 levels may have a transient increase, before becoming subnormal during severe illness. Correspondingly, in the majority of cases calculated sum activity of peripheral deiodinases (SPINA-GD) is reduced.[7][20][21][22] Generally the levels of free T3 will be lowered, followed by the lowering of free T4 in more severe disease. Several studies described elevated concentrations of 3,5-T2, an active thyroid hormone, in NTIS.[22][23] 3,5-T2 levels were also observed to correlate with concentrations of rT3 (reverse T3)[22] in patients with euthyroid sick syndrome. NTIS is a component of a complex endocrine adaptation process, so affected patients might also have hyperprolactinemia and elevated levels of corticosteroids (especially cortisol) and growth hormone.[citation needed] NTIS can be difficult to distinguish from other forms of thyroid dysfunction in the hospital setting. Both NTIS and primary hypothyroidism may have reduced fT3 and fT4, and elevated TSH (which is common in the hospital, during the recovery phase of NTIS).[2] Prescribing thyroxine to treat this may lead to lifelong thyroid overtreatment.[2] Hyperthyroidism may be assumed due to decreased TSH and a transient fT4 increase. In some cases, this can be distinguished from NTIS by a thyroid ultrasound, which is commonly available in the hospital intensive care unit.[2] NTIS looks similar to central hypopituitarism; both frequently have reduced TSH and thyroid hormone levels.[2] ## Treatment[edit] Debate is ongoing as to whether NTIS is an adaptive or maladaptive mechanism in response to physiological stress.[3][5][10] Some sources indicate that NTIS is beneficial as an acute-phase response, but detrimental during the chronic phase of illness.[2] Several trials have investigated a possible therapy for NTIS, but they yielded inconsistent and partly contradictory results. This may be due to the heterogeneity of investigated populations, and to the lack of a consistent definition of NTIS.[24] Administering exogenous T3 and T4 has variable results,[3][10] but overall seems to confer no improvements to health outcome.[5] Administering TRH to patients with chronic illness, however, seems to normalize thyroid levels and improve catabolic function,[5] although whether this is beneficial is unclear. When NTIS is caused by the normal fasting response to illness, early parenteral nutrition has been shown to attenuate alterations in thyroid hormone (TSH, T3, T4, rT3) levels, whereas late parenteral nutrition exacerbates it.[10] Late parenteral nutrition, though, also reduced complications and accelerated recovery in one study.[10] ## History[edit] In 1968, a reduced T4 half-life in athletes was discovered. This was the first awareness of thyroid hormone concentration alterations that were not a result of thyroid gland or pituitary dysfunction. In 1971, they also found a transient increase in T4 during bicycle training.[2] In 1973, Rothenbuchner et al. discovered that starvation is correlated with reduced T3 concentration. Following this, a similar phenotype was noted in patients with critical illness, tumors, and uremia.[2] The alternative phenotype of type-2 thyroid allostasis was first predicted in 1968, when John W. Mason expected the concentrations of thyroid hormones to rise in situations of psychosocial stress.[25] Mason's postulate was later confirmed by numerous studies.[26][27][28][29][30][31][32][excessive citations] ## See also[edit] * Thyroid storm ## References[edit] 1. ^ a b Hershman JM. "Euthyroid Sick Syndrome: Thyroid Disorders". Merck Manual Professional. Merck & Co., Inc. Retrieved 2009-03-29. 2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Chatzitomaris A, Hoermann R, Midgley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH, Dietrich JW (20 July 2017). "Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8: 163. doi:10.3389/fendo.2017.00163. PMC 5517413. PMID 28775711. 3. ^ a b c d e f g h i j k l m n Pappa TA, Vagenakis AG, Alevizaki M (February 2011). "The nonthyroidal illness syndrome in the non-critically ill patient". European Journal of Clinical Investigation. 41 (2): 212–20. doi:10.1111/j.1365-2362.2010.02395.x. PMID 20964678. S2CID 24529523. 4. ^ Dietrich, J. W.; Ackermann, A.; Kasippillai, A.; Kanthasamy, Y.; Tharmalingam, T.; Urban, A.; Vasileva, S.; Schildhauer, T. A.; Klein, H. H.; Stachon, A.; Hering, S. (19 September 2019). "Adaptive Veränderungen des Schilddrüsenstoffwechsels als Risikoindikatoren bei Traumata". Trauma und Berufskrankheit. 21 (4): 260–267. doi:10.1007/s10039-019-00438-z. S2CID 202673793. 5. ^ a b c d e f g h i j k l m n o p q r s t u v w Warner MH, Beckett GJ (April 2010). "Mechanisms behind the non-thyroidal illness syndrome: an update". The Journal of Endocrinology. 205 (1): 1–13. doi:10.1677/JOE-09-0412. PMID 20016054. 6. ^ Abelleira E, De Cross GA, Pitoia F (2014). "[Thyroid dysfunction in adults infected by human immunodeficiency virus]". Medicina. 74 (4): 315–20. PMID 25188661. 7. ^ a b Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J (February 2013). "Nonthyroidal illness syndrome: is it far away from Crohn's disease?". Journal of Clinical Gastroenterology. 47 (2): 153–9. doi:10.1097/MCG.0b013e318254ea8a. PMID 22874844. S2CID 35344744. 8. ^ Ruiz-Núñez B, Tarasse R, Vogelaar EF, Janneke Dijck-Brouwer DA, Muskiet FA (20 March 2018). "Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case-Control Study". Frontiers in Endocrinology. 9: 97. doi:10.3389/fendo.2018.00097. PMC 5869352. PMID 29615976. 9. ^ Hoermann R, Midgley JE, Larisch R, Dietrich JW (2015). "Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment". Frontiers in Endocrinology. 6: 177. doi:10.3389/fendo.2015.00177. PMC 4653296. PMID 26635726. 10. ^ a b c d e f g h i j k Fliers E, Bianco AC, Langouche L, Boelen A (October 2015). "Thyroid function in critically ill patients". The Lancet. Diabetes & Endocrinology. 3 (10): 816–25. doi:10.1016/S2213-8587(15)00225-9. PMC 4979220. PMID 26071885. 11. ^ de Vries EM, Fliers E, Boelen A (June 2015). "The molecular basis of the non-thyroidal illness syndrome". The Journal of Endocrinology. 225 (3): R67–81. doi:10.1530/JOE-15-0133. PMID 25972358. 12. ^ a b Alhazmi, Ayman S; Alomey, Anas; Almalki, Hilal; Almehmadi, Mazen; Albshri, Mohammad; Algarni, Naif; Almutiri, Sultan (December 2018). "Effect of High Altitude on Thyroid and Thyroid Stimulating Hormones Levels in Taif City" (PDF). Acta Scientific Nutritional Health. Acta Scientific. 2 (12). Retrieved 22 September 2019. 13. ^ Choi, Juli; Kim, Ji-eun; Kim, Tae-Kyung; Park, Jin-Young; Lee, Jung-Eun; Kim, Hannah; Lee, Eun-Hwa; Han, Pyung-Lim (October 2015). "TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors". Neuropharmacology. 97: 346–356. doi:10.1016/j.neuropharm.2015.03.030. PMID 26107116. S2CID 1839062. 14. ^ Wittmann, Gábor; Lechan, Ronald M.; Liposits, Zsolt; Fekete, Csaba (March 2005). "Glutamatergic innervation of corticotropin-releasing hormone- and thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus of the rat". Brain Research. 1039 (1–2): 53–62. doi:10.1016/j.brainres.2005.01.090. PMID 15781046. S2CID 14375998. 15. ^ Kim, BW; Daniels, GH; Harrison, BJ; Price, A; Harney, JW; Larsen, PR; Weetman, AP (February 2003). "Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels". The Journal of Clinical Endocrinology and Metabolism. 88 (2): 594–8. doi:10.1210/jc.2002-020921. PMID 12574186. 16. ^ Miyauchi, A; Takamura, Y; Ito, Y; Miya, A; Kobayashi, K; Matsuzuka, F; Amino, N; Toyoda, N; Nomura, E; Nishikawa, M (June 2008). "3,5,3'-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma". The Journal of Clinical Endocrinology and Metabolism. 93 (6): 2239–42. doi:10.1210/jc.2007-2282. PMID 18397985. 17. ^ Abid, SA; Stack BC, Jr; Bodenner, DL (2014). "Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review". Case Reports in Endocrinology. 2014: 584513. doi:10.1155/2014/584513. PMC 4220571. PMID 25400957. 18. ^ Yu, Run (2018). "High T3 Syndrome Associated with Metastatic Papillary and Poorly Differentiated Thyroid Cancer" (PDF). Archives of Diabetes and Endocrine System. 1 (1): 10–12. Retrieved 22 September 2019. 19. ^ Hackney, AC; Feith, S; Pozos, R; Seale, J (April 1995). "Effects of high altitude and cold exposure on resting thyroid hormone concentrations". Aviation, Space, and Environmental Medicine. 66 (4): 325–9. PMID 7794224. 20. ^ Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (August 2005). "Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure". Endocrine. 27 (3): 283–8. doi:10.1385/ENDO:27:3:283. PMID 16230785. S2CID 25630198. 21. ^ Han G, Ren J, Liu S, Gu G, Ren H, Yan D, Chen J, Wang G, Zhou B, Wu X, Yuan Y, Li J (September 2013). "Nonthyroidal illness syndrome in enterocutaneous fistulas". American Journal of Surgery. 206 (3): 386–92. doi:10.1016/j.amjsurg.2012.12.011. PMID 23809674. 22. ^ a b c Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I (June 2015). "Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling". European Thyroid Journal. 4 (2): 129–37. doi:10.1159/000381543. PMC 4521060. PMID 26279999. 23. ^ Pinna G, Meinhold H, Hiedra L, Thoma R, Hoell T, Gräf KJ, Stoltenburg-Didinger G, Eravci M, Prengel H, Brödel O, Finke R, Baumgartner A (May 1997). "Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors". The Journal of Clinical Endocrinology and Metabolism. 82 (5): 1535–42. doi:10.1210/jcem.82.5.3939. PMID 9141546. 24. ^ Dietrich JW, Stachon A, Antic B, Klein HH, Hering S (October 2008). "The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome". BMC Endocrine Disorders. 8: 13. doi:10.1186/1472-6823-8-13. PMC 2576461. PMID 18851740. 25. ^ MASON, JOHN W. (September 1968). "A Review of Psychoendocrine Research on the Pituitary-Adrenal Cortical System". Psychosomatic Medicine. 30 (5): 576–607. doi:10.1097/00006842-196809000-00020. PMID 4303377. S2CID 26755389. 26. ^ Levy, RP; Jensen, JB; Laus, VG; Agle, DP; Engel, IM (November 1981). "Serum thyroid hormone abnormalities in psychiatric disease". Metabolism: Clinical and Experimental. 30 (11): 1060–4. doi:10.1016/0026-0495(81)90048-2. PMID 7289880. 27. ^ Spratt, DI; Pont, A; Miller, MB; McDougall, IR; Bayer, MF; McLaughlin, WT (July 1982). "Hyperthyroxinemia in patients with acute psychiatric disorders". The American Journal of Medicine. 73 (1): 41–8. doi:10.1016/0002-9343(82)90922-6. PMID 6807087. 28. ^ Chopra, IJ; Solomon, DH; Huang, TS (May 1990). "Serum thyrotropin in hospitalized psychiatric patients: evidence for hyperthyrotropinemia as measured by an ultrasensitive thyrotropin assay". Metabolism: Clinical and Experimental. 39 (5): 538–43. doi:10.1016/0026-0495(90)90014-4. PMID 2336036. 29. ^ Wang, S; Mason, J; Southwick, S; Johnson, D; Lubin, H; Charney, D (July–August 1995). "Relationships between thyroid hormones and symptoms in combat-related posttraumatic stress disorder". Psychosomatic Medicine. 57 (4): 398–402. doi:10.1097/00006842-199507000-00012. PMID 7480570. S2CID 20905167. 30. ^ Friedman, MJ; Wang, S; Jalowiec, JE; McHugo, GJ; McDonagh-Coyle, A (15 May 2005). "Thyroid hormone alterations among women with posttraumatic stress disorder due to childhood sexual abuse". Biological Psychiatry. 57 (10): 1186–92. doi:10.1016/j.biopsych.2005.01.019. PMID 15866559. S2CID 23455036. 31. ^ Mason, J; Southwick, S; Yehuda, R; Wang, S; Riney, S; Bremner, D; Johnson, D; Lubin, H; Blake, D; Zhou, G (August 1994). "Elevation of serum free triiodothyronine, total triiodothyronine, thyroxine-binding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder". Archives of General Psychiatry. 51 (8): 629–41. doi:10.1001/archpsyc.1994.03950080041006. PMID 8042912. 32. ^ Karlović, D; Marusić, S; Martinac, M (30 June 2004). "Increase of serum triiodothyronine concentration in soldiers with combat-related chronic post-traumatic stress disorder with or without alcohol dependence". Wiener klinische Wochenschrift. 116 (11–12): 385–90. doi:10.1007/BF03040918. PMID 15291291. S2CID 26011489. ## Further reading[edit] * McIver B, Gorman CA (February 1997). "Euthyroid sick syndrome: an overview". Thyroid. 7 (1): 125–32. doi:10.1089/thy.1997.7.125. PMID 9086580. ## External links[edit] Classification D * ICD-10: E07.8 * ICD-9-CM: 790.94 * MeSH: D005067 External resources * eMedicine: med/753 * v * t * e Thyroid disease Hypothyroidism * Iodine deficiency * Cretinism * Congenital hypothyroidism * Myxedema * Myxedema coma * Euthyroid sick syndrome * Signs and symptoms * Queen Anne's sign * Woltman sign * Thyroid dyshormonogenesis * Pickardt syndrome Hyperthyroidism * Hyperthyroxinemia * Thyroid hormone resistance * Familial dysalbuminemic hyperthyroxinemia * Hashitoxicosis * Thyrotoxicosis factitia * Thyroid storm Graves' disease * Signs and symptoms * Abadie's sign of exophthalmic goiter * Boston's sign * Dalrymple's sign * Stellwag's sign * lid lag * Griffith's sign * Möbius sign * Pretibial myxedema * Graves' ophthalmopathy Thyroiditis * Acute infectious * Subacute * De Quervain's * Subacute lymphocytic * Palpation * Autoimmune/chronic * Hashimoto's * Postpartum * Riedel's Enlargement * Goitre * Endemic goitre * Toxic nodular goitre * Toxic multinodular goiter * Thyroid nodule * Colloid nodule *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Euthyroid sick syndrome

c0015190

wikipedia

https://en.wikipedia.org/wiki/Euthyroid_sick_syndrome

{"mesh": ["D005067"], "umls": ["C0015190"], "wikidata": ["Q1378921"]}

Agnathia (also termed hypognathous)[1] is absence of a portion or the entirety of one or both jaws.[1][2] It is a very rare condition.[1] ## See also[edit] * Micrognathia ## References[edit] 1. ^ a b c Ghom AG; Ghom SA (30 September 2014). Textbook of Oral Medicine. JP Medical Ltd. p. 125. ISBN 978-93-5152-303-1. 2. ^ Rajendran A; Sundaram S (10 February 2014). Shafer's Textbook of Oral Pathology (7th ed.). Elsevier Health Sciences APAC. p. 12. ISBN 978-81-312-3800-4. * v * t * e Oral and maxillofacial pathology Lips * Cheilitis * Actinic * Angular * Plasma cell * Cleft lip * Congenital lip pit * Eclabium * Herpes labialis * Macrocheilia * Microcheilia * Nasolabial cyst * Sun poisoning * Trumpeter's wart Tongue * Ankyloglossia * Black hairy tongue * Caviar tongue * Crenated tongue * Cunnilingus tongue * Fissured tongue * Foliate papillitis * Glossitis * Geographic tongue * Median rhomboid glossitis * Transient lingual papillitis * Glossoptosis * Hypoglossia * Lingual thyroid * Macroglossia * Microglossia * Rhabdomyoma Palate * Bednar's aphthae * Cleft palate * High-arched palate * Palatal cysts of the newborn * Inflammatory papillary hyperplasia * Stomatitis nicotina * Torus palatinus Oral mucosa – Lining of mouth * Amalgam tattoo * Angina bullosa haemorrhagica * Behçet's disease * Bohn's nodules * Burning mouth syndrome * Candidiasis * Condyloma acuminatum * Darier's disease * Epulis fissuratum * Erythema multiforme * Erythroplakia * Fibroma * Giant-cell * Focal epithelial hyperplasia * Fordyce spots * Hairy leukoplakia * Hand, foot and mouth disease * Hereditary benign intraepithelial dyskeratosis * Herpangina * Herpes zoster * Intraoral dental sinus * Leukoedema * Leukoplakia * Lichen planus * Linea alba * Lupus erythematosus * Melanocytic nevus * Melanocytic oral lesion * Molluscum contagiosum * Morsicatio buccarum * Oral cancer * Benign: Squamous cell papilloma * Keratoacanthoma * Malignant: Adenosquamous carcinoma * Basaloid squamous carcinoma * Mucosal melanoma * Spindle cell carcinoma * Squamous cell carcinoma * Verrucous carcinoma * Oral florid papillomatosis * Oral melanosis * Smoker's melanosis * Pemphigoid * Benign mucous membrane * Pemphigus * Plasmoacanthoma * Stomatitis * Aphthous * Denture-related * Herpetic * Smokeless tobacco keratosis * Submucous fibrosis * Ulceration * Riga–Fede disease * Verruca vulgaris * Verruciform xanthoma * White sponge nevus Teeth (pulp, dentin, enamel) * Amelogenesis imperfecta * Ankylosis * Anodontia * Caries * Early childhood caries * Concrescence * Failure of eruption of teeth * Dens evaginatus * Talon cusp * Dentin dysplasia * Dentin hypersensitivity * Dentinogenesis imperfecta * Dilaceration * Discoloration * Ectopic enamel * Enamel hypocalcification * Enamel hypoplasia * Turner's hypoplasia * Enamel pearl * Fluorosis * Fusion * Gemination * Hyperdontia * Hypodontia * Maxillary lateral incisor agenesis * Impaction * Wisdom tooth impaction * Macrodontia * Meth mouth * Microdontia * Odontogenic tumors * Keratocystic odontogenic tumour * Odontoma * Dens in dente * Open contact * Premature eruption * Neonatal teeth * Pulp calcification * Pulp stone * Pulp canal obliteration * Pulp necrosis * Pulp polyp * Pulpitis * Regional odontodysplasia * Resorption * Shovel-shaped incisors * Supernumerary root * Taurodontism * Trauma * Avulsion * Cracked tooth syndrome * Vertical root fracture * Occlusal * Tooth loss * Edentulism * Tooth wear * Abrasion * Abfraction * Acid erosion * Attrition Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures * Cementicle * Cementoblastoma * Gigantiform * Cementoma * Eruption cyst * Epulis * Pyogenic granuloma * Congenital epulis * Gingival enlargement * Gingival cyst of the adult * Gingival cyst of the newborn * Gingivitis * Desquamative * Granulomatous * Plasma cell * Hereditary gingival fibromatosis * Hypercementosis * Hypocementosis * Linear gingival erythema * Necrotizing periodontal diseases * Acute necrotizing ulcerative gingivitis * Pericoronitis * Peri-implantitis * Periodontal abscess * Periodontal trauma * Periodontitis * Aggressive * As a manifestation of systemic disease * Chronic * Perio-endo lesion * Teething Periapical, mandibular and maxillary hard tissues – Bones of jaws * Agnathia * Alveolar osteitis * Buccal exostosis * Cherubism * Idiopathic osteosclerosis * Mandibular fracture * Microgenia * Micrognathia * Intraosseous cysts * Odontogenic: periapical * Dentigerous * Buccal bifurcation * Lateral periodontal * Globulomaxillary * Calcifying odontogenic * Glandular odontogenic * Non-odontogenic: Nasopalatine duct * Median mandibular * Median palatal * Traumatic bone * Osteoma * Osteomyelitis * Osteonecrosis * Bisphosphonate-associated * Neuralgia-inducing cavitational osteonecrosis * Osteoradionecrosis * Osteoporotic bone marrow defect * Paget's disease of bone * Periapical abscess * Phoenix abscess * Periapical periodontitis * Stafne defect * Torus mandibularis Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities * Bruxism * Condylar resorption * Mandibular dislocation * Malocclusion * Crossbite * Open bite * Overbite * Overeruption * Overjet * Prognathia * Retrognathia * Scissor bite * Maxillary hypoplasia * Temporomandibular joint dysfunction Salivary glands * Benign lymphoepithelial lesion * Ectopic salivary gland tissue * Frey's syndrome * HIV salivary gland disease * Necrotizing sialometaplasia * Mucocele * Ranula * Pneumoparotitis * Salivary duct stricture * Salivary gland aplasia * Salivary gland atresia * Salivary gland diverticulum * Salivary gland fistula * Salivary gland hyperplasia * Salivary gland hypoplasia * Salivary gland neoplasms * Benign: Basal cell adenoma * Canalicular adenoma * Ductal papilloma * Monomorphic adenoma * Myoepithelioma * Oncocytoma * Papillary cystadenoma lymphomatosum * Pleomorphic adenoma * Sebaceous adenoma * Malignant: Acinic cell carcinoma * Adenocarcinoma * Adenoid cystic carcinoma * Carcinoma ex pleomorphic adenoma * Lymphoma * Mucoepidermoid carcinoma * Sclerosing polycystic adenosis * Sialadenitis * Parotitis * Chronic sclerosing sialadenitis * Sialectasis * Sialocele * Sialodochitis * Sialosis * Sialolithiasis * Sjögren's syndrome Orofacial soft tissues – Soft tissues around the mouth * Actinomycosis * Angioedema * Basal cell carcinoma * Cutaneous sinus of dental origin * Cystic hygroma * Gnathophyma * Ludwig's angina * Macrostomia * Melkersson–Rosenthal syndrome * Microstomia * Noma * Oral Crohn's disease * Orofacial granulomatosis * Perioral dermatitis * Pyostomatitis vegetans Other * Eagle syndrome * Hemifacial hypertrophy * Facial hemiatrophy * Oral manifestations of systemic disease *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Agnathia

c0685775

wikipedia

https://en.wikipedia.org/wiki/Agnathia

{"wikidata": ["Q21071557"]}

For a discussion of genetic heterogeneity of coronary heart disease (CHD), see 607339. Mapping McPherson et al. (2007) used genomewide association scanning to identify a 58-kb interval on chromosome 9p21 that was consistently associated with coronary heart disease in 6 independent samples (more than 23,000 participants) from 4 Caucasian populations. To minimize false positive associations without unduly sacrificing statistical power, McPherson et al. (2007) designed the study to comprise 3 sequential case-control comparisons performed at a nominal significance threshold of P is less than 0.025. The 3 case-control comparisons identified 2 SNPs, rs10757274 and rs2383206, associated with CHD that were located within 20 kb of each other on chromosome 9p21 and were in strong linkage disequilibrium. In validation studies using 3 additional independent cohorts, both SNPs were significantly associated with CHD. Fine mapping studies indicated that the risk allele defined by rs10757274 and rs2383206 comprises a haplotype that spans approximately 58 kb. This interval, which is located near the CDKN2A (600160) and CDKN2B (610347) genes, contained no annotated genes and was not associated with established CHD risk factors such as plasma lipoproteins, hypertension, or diabetes. Resequencing of the 58-kb interval in 2 homozygotes for the risk allele and in 1 homozygote for the reference allele revealed 66 polymorphisms (SNPs plus small insertions or deletions), of which 35 were specific to the risk allele. Only 1 of these variants, a copy number variation in a run of 9 consecutive CAT repeats, mapped to a spliced transcript (BI765545) that appeared to be part of a large noncoding RNA. The mechanistic basis for the association between the risk allele defined by rs10757274 and rs2383206 and coronary heart disease was not known. Homozygotes for the risk allele were estimated to make up 20 to 25% of Caucasians, and have an approximately 30 to 40% increased risk of CHD. Helgadottir et al. (2007) performed a genomewide association study in a total of 4,587 cases and 12,767 controls from the Icelandic population and identified 3 correlated SNPs. To replicate the observed associations, the authors genotyped the 3 SNPs in an additional 665 Icelandic myocardial infarction (MI) cases and 3,533 controls, and in 3 case-control sample sets of European descent from 3 cities in the United States. The SNP rs10757278 emerged as having the strongest association with the disease. With results from all groups combined, relative to noncarriers, the odds ratios for heterozygous and homozygous carriers of the risk allele G were 1.26 and 1.64, respectively. The corresponding odds ratio for early-onset cases was determined to be 2.02 for homozygous carriers of the risk allele. Assuming an allele frequency of 45.3%, the population-attributable risk is 21% for MI in general and 31% for early-onset cases. The Wellcome Trust Case Control Consortium (2007) described a joint genomewide association study using the Affymetrix GeneChip 500K Mapping Array Set, undertaken in the British population, which examined approximately 2,000 individuals for each of 7 major diseases and a shared set of approximately 3,000 controls. This analysis identified a powerful association with coronary artery disease on chromosome 9p21.3. Although the strongest signal was seen at rs1333049 (P = 1.8 x 10(-14)), associations were seen for SNPs across more than 100 kb. Helgadottir et al. (2008) found that, in addition to coronary artery disease, the rs10757278-G SNP is associated with abdominal aortic aneurysm (AAA3; 611891) (odds ratio = 1.31) and intracranial aneurysm (ANIB6; 611891) (odds ratio = 1.29). This was said to be the first variant to be described that affects the risk of AAA and intracranial aneurysm in many populations. Hinohara et al. (2008) evaluated the association of rs1333049 with coronary artery disease (CAD) in 604 Japanese patients and 1,151 controls and in 679 Korean patients and 706 controls, and found a significant association in both groups (odds ratio = 1.30 and 1.19, and p = 0.00027 and 0.025, respectively). Noting that previous studies had focused on Caucasian populations, the authors concluded that chromosome 9p21 is also a susceptibility locus for CAD in East Asian patients. In a case-control study of 416 Italian MI patients and 308 controls, Shen et al. (2008) found significant association with 4 SNPs on chromosome 9p21 (rs10757274, rs2383206, rs2383207, and 10757278) that remained significant after adjusting for covariates for MI, and identified a GGGG risk haplotype and an AAAA protective haplotype. When the case cohort was divided into patients with a positive family history and those without, significant association was identified only in the group with a positive family history. Shen et al. (2008) concluded that chromosome 9p21 confers risk for development of MI in the Italian population. In a European case-control study involving 4,251 patients with coronary artery disease and 4,443 controls, Broadbent et al. (2008) replicated association (p values ranging from 3 x 10(-11) to 8 x 10(-13); odds ratios from 1.26 to 1.29) for 7 SNPs on chromosome 9p21 (rs10116277, rs6475606, rs10757274, rs2383206, rs2383207, rs10757278, and rs1333049). The authors showed that the consistent association was a result of a 'yin-yang' haplotype pattern spanning 53 kb, and noted that a large antisense noncoding RNA gene (CDKN2BAS; 613149) colocates with the high-risk haplotype and is expressed in tissues and cell types that are affected by atherosclerosis. Simultaneous testing of CAD and type 2 diabetes-associated SNPs at chromosome 9p21 (see 125853) indicated that these associations were independent of each other. Harismendy et al. (2011) identified 33 enhancers in 9p21; the interval is the second densest gene desert for predicted enhancers and 6 times denser than the whole genome (P less than 6.55 x 10(-33)). The CAD risk alleles of SNPs rs10811656 and rs10757278 are located in one of these enhancers and disrupt a binding site for STAT1 (600555). Lymphoblastoid cell lines homozygous for the CAD risk haplotype show no binding of STAT1, and in lymphoblastoid cell lines homozygous for the CAD nonrisk haplotype, binding of STAT1 inhibits CDKN2BAS expression, which is reversed by short interfering RNA knockdown of STAT1. Using a new, open-ended approach to detect long-distance interactions, Harismendy et al. (2011) found that in human vascular endothelial cells the enhancer interval containing the CAD locus physically interacts with the CDKN2A/B locus (see 600431), the MTAP gene (156540), and an interval downstream of IFNA21 (147584). In human vascular endothelial cells, interferon-gamma (147570) activation strongly affects the structure of the chromatin and the transcriptional regulation in the 9p21 locus, including STAT1 binding, long-range enhancer interactions, and altered expression of neighboring genes. Harismendy et al. (2011) concluded that their findings established a link between CAD genetic susceptibility and the response to inflammatory signaling in a vascular cell type. Animal Model Visel et al. (2010) showed that deletion of the 70-kb noncoding interval on mouse chromosome 4 orthologous to the chromosome 9p21 interval associated with human coronary artery disease (CAD) affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Mice with homozygous deletion of the 70-kb interval (delta-70-kb) were viable but showed increased mortality both during development and as adults. Cardiac expression of 2 genes near the noncoding interval, Cdkn2a (600160) and Cdkn2b (600431), was severely reduced in delta-70-kb homozygous mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allele-specific expression of Cdkn2b transcripts in heterozygous mice showed that the deletion affects expression through a cis-acting mechanism. Primary cultures of aortic smooth muscle cells from homozygous delta-70-kb mice exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Visel et al. (2010) concluded that, taken together, their results provided direct evidence that the CAD risk interval has a pivotal role in the regulation of cardiac CDKN2A/B expression, and suggested that this region affects coronary artery disease progression by altering the dynamics of vascular cell proliferation. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

CORONARY HEART DISEASE, SUSCEPTIBILITY TO, 8

c1970158

omim

https://www.omim.org/entry/611139

{"omim": ["611139"]}

A number sign (#) is used with this entry because of evidence that 46,XX sex reversal with dysgenesis of kidney, adrenals, and lungs (SERKAL) is caused by homozygous mutation in the WNT4 gene (603490) on chromosome 1p36. One such family has been reported. Clinical Features Mandel et al. (2008) studied a consanguineous kindred of Arab Muslim origin. The family had been followed since the birth of an infant who died of type 1 citrullinemia (215700) at age 4 days. The parents were second cousins. Three affected fetuses showed largely overlapping features including female sex reversal and dysgenesis of kidneys, adrenals, and lungs, given the acronym of SERKAL syndrome. In the case of all 3 affected fetuses, pregnancy was terminated because of the finding of renal agenesis. Molecular Genetics Given the similarities between the findings in these cases and a WNT4 knockout mouse model (Vainio et al., 1999; Heikkila et al., 2005), Mandel et al. (2008) genotyped all available family members for microsatellite markers spanning the WNT4 locus. The affected fetus from which DNA was available displayed a homozygous haplotype, which was found to be carried in heterozygous state by all parents and unaffected sibs, suggesting the existence of a homozygous mutation in WNT4 in the affected fetus. The mutation was found to be a homozygous transition resulting in the amino acid substitution A114V (603490.0002). The mutation resulted in markedly reduced WNT4 mRNA levels in vivo and in vitro and downregulated WNT4-dependent inhibition of beta-catenin (116806) degradation. INHERITANCE \- Autosomal recessive GROWTH Other \- Intrauterine growth retardation HEAD & NECK Ears \- Low-set ears Mouth \- Cleft lip \- Cleft palate CARDIOVASCULAR Heart \- Ventricular septal defect Vascular \- Pulmonary artery stenosis RESPIRATORY Lung \- Small lungs \- Hypoplastic lungs CHEST Diaphragm \- Diaphragmatic hernia GENITOURINARY External Genitalia (Male) \- Curved penis \- Hypospadias Internal Genitalia (Male) \- Ovotestis (in 1 fetus) Kidneys \- Kidney agenesis/dysgenesis Ureters \- Thin ureters Bladder \- Hypoplastic bladder ENDOCRINE FEATURES \- Adrenal agenesis/dysgenesis PRENATAL MANIFESTATIONS Amniotic Fluid \- Oligohydramnios LABORATORY ABNORMALITIES \- 46,XX male (in 1 fetus) MISCELLANEOUS \- Based on 3 fetuses in 1 consanguineous family (last curated November 2016) \- All 3 pregnancies terminated MOLECULAR BASIS \- Caused by mutation in the wingless-type MMTV integration site family, member 4 (WNT4, 603490.0002 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

46,XX SEX REVERSAL WITH DYSGENESIS OF KIDNEYS, ADRENALS, AND LUNGS

c2678492

omim

https://www.omim.org/entry/611812

{"mesh": ["C567517"], "omim": ["611812"], "orphanet": ["139466"], "synonyms": ["Alternative titles", "SERKAL SYNDROME"]}

Baboon syndrome SpecialtyDermatology Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), more popularly known as Baboon syndrome because of its resemblance to the distinctive red buttocks displayed by female baboons, is a systemic contact dermatitis characterized by well-demarcated patches of erythema distributed symmetrically on the buttocks.[1] The cause of the syndrome may be drug-related, i.e. induced by systemic administration of hydroxyzine[2] penicillin,[3] iodinated radio contrast media[4] and others. ## Contents * 1 Symptoms and signs * 2 Cause * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 See also * 7 References ## Symptoms and signs[edit] The typical rash commonly appears on buttocks. This then resembles the colour of a baboon's buttocks. Other areas like upper inner thigh and armpits, may be affected by the rash. The rashes are red and well-defined. The presentation is typically symmetrical and not associated with systemic symptoms.[5] ## Cause[edit] This section is empty. You can help by adding to it. (April 2017) ## Diagnosis[edit] This section is empty. You can help by adding to it. (April 2017) ## Treatment[edit] Treatment of symmetrical drug related intertriginous and flexural exanthema involves identifying and stopping the causative agent. Topical steroids can help to reduce the redness.[6] ## Epidemiology[edit] Baboon syndrome affects both sexes equally, and can occur at any age, but seems to be more common in childhood than in adulthood.[7] ## See also[edit] * Airbag dermatitis * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ Akkari, H.; Belhadjali, H.; Youssef, M.; Mokni, S.; Zili, J. (May 2013). "Baboon syndrome induced by hydroxyzine". Indian J Dermatol. 58 (3): 244. doi:10.4103/0019-5154.110871. PMC 3667318. PMID 23723506. 3. ^ Handisurya, A.; Stingl, G.; Wöhrl, S. (Apr 2009). "SDRIFE (baboon syndrome) induced by penicillin". Clin Exp Dermatol. 34 (3): 355–7. doi:10.1111/j.1365-2230.2008.02911.x. PMID 18699835. 4. ^ Arnold, AW.; Hausermann, P.; Bach, S.; Bircher, AJ. (2007). "Recurrent flexural exanthema (SDRIFE or baboon syndrome) after administration of two different iodinated radio contrast media". Dermatology. 214 (1): 89–93. doi:10.1159/000096920. PMID 17191055. 5. ^ Utaş, S.; Ferahbaş, A. (2009). "Baboon syndrome and segmental vitiligo coexistence". The Turkish Journal of Pediatrics. 51 (4): 392–4. PMID 19950853. 6. ^ "Symmetrical drug related intertriginous and flexural exanthema | DermNet NZ". www.dermnetnz.org. Retrieved 2019-04-19. 7. ^ Moreno-Ramírez, D.; García-Bravo, B.; Pichardo, AR.; Rubio, FP.; Martínez, FC. (2004). "Baboon syndrome in childhood: easy to avoid, easy to diagnose, but the problem continues". Pediatr Dermatol. 21 (3): 250–3. doi:10.1111/j.0736-8046.2004.21313.x. PMID 15165206. * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Baboon syndrome

c0406284

wikipedia

https://en.wikipedia.org/wiki/Baboon_syndrome

{"umls": ["C0406284"], "icd-10": ["L25.1", "L24.4"], "wikidata": ["Q797738"]}

Dextrocardia is a condition in which the heart is located in the right side of the chest instead of the left. It is usually present from birth (congenital). There are several types of dextrocardia. The simplest type occurs when the shape and structure of the heart is a mirror image of a normal heart. Other types of dextrocardia may involve defects of the walls of the heart, nearby blood vessels, or other organs in the abdomen. Chest X-raxys and echocardiograms can be used to determine which type of dextrocardia is present. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Dextrocardia

c0011813

gard

https://rarediseases.info.nih.gov/diseases/1827/dextrocardia

{"mesh": ["D003914"], "umls": ["C0011813"], "synonyms": []}

A rare syndromic genetic deafness characterized by profound congenital bilateral sensorineural deafness, developmental delay, moderate intellectual disability, generalized delay in bone maturation, short stature, epiphyseal dysplasia particularly of the capital femoral epiphyses, and mild dysmorphic facial features such as prominent forehead and small, pointed chin. Bilateral obstruction of lacrimal ducts and inguinal and umbilical hernias have also been described. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Deafness-epiphyseal dysplasia-short stature syndrome

c1832438

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3218

{"gard": ["1688"], "mesh": ["C535928"], "omim": ["601351"], "umls": ["C1832438"], "synonyms": ["Chitty-Hall-Baraitser syndrome", "Hearing loss-epiphyseal dysplasia-short stature syndrome"]}

Autosomal dominant multiple pterygium syndrome Other namesDistal arthrogryposis type 8[1] SpecialtyDermatology Multiple pterygium syndrome is a cutaneous condition inherited in an autosomal dominant fashion.[2] ## Contents * 1 Society * 2 See also * 3 References * 4 External links ## Society[edit] Musician Patrick Henry Hughes has a type of this condition.[3] ## See also[edit] * Popliteal pterygium syndrome * List of cutaneous conditions * Datagenno - Escobar Syndrome ## References[edit] 1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Autosomal dominant multiple pterygium syndrome". www.orpha.net. Retrieved 28 September 2019. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 3. ^ Louisville Magazine ## External links[edit] Classification D * ICD-10: Q79.8 * OMIM: 178110 * MeSH: C537377 External resources * Orphanet: 65743 This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Autosomal dominant multiple pterygium syndrome

c0265261

wikipedia

https://en.wikipedia.org/wiki/Autosomal_dominant_multiple_pterygium_syndrome

{"gard": ["7111"], "mesh": ["C537377"], "umls": ["C0265261"], "orphanet": ["294060", "2990"], "wikidata": ["Q16889762"]}

A rare, genetic, neuromuscular disease characterized by progressive, symmetrical, moderate to severe, distal muscle weakness and atrophy, without sensory involvement, first affecting the lower limbs (towards the end of the first decade) and then involving (within two years) the upper extremities. Patients typically develop foot drop, pes varus, hammer toes and claw hands. Pyramidal tract signs (such as brisk knee reflexes and positive Babinski sign) with absent ankle reflexes are initially associated but regress as disease stabilizes (~10 years after onset). *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Distal hereditary motor neuropathy, Jerash type

c1854023

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139552

{"gard": ["10133"], "mesh": ["C535715"], "omim": ["605726"], "umls": ["C1854023"], "icd-10": ["G12.2"], "synonyms": ["Autosomal recessive distal spinal muscular atrophy type 2", "dHMNJ"]}

A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-57 (MRD57) is caused by heterozygous mutation in the TLK2 gene (608439) on chromosome 17q23. Description MRD57 is an autosomal dominant neurodevelopmental disorder with a highly variable phenotype. Most affected individuals have delayed psychomotor development apparent in infancy or early childhood, language delay, and behavioral abnormalities. Additional features may include hypotonia, feeding problems, gastrointestinal issues, and dysmorphic facial features (summary by Reijnders et al., 2018). Clinical Features Lelieveld et al. (2016) reported 2 patients with MRD57 associated with de novo heterozygous variants in the TLK2 gene. The patients were ascertained from a cohort of 820 parent-child trios with intellectual disability. A 20-year-old man (patient 17), born of consanguineous Turkish parents, had delayed psychomotor development with language delay and behavioral abnormalities, including tantrums and periods of hyperventilation. Additional features included myopia, strabismus, and diarrhea. Dysmorphic features included short forehead, upslanting palpebral fissures, epicanthal folds, hypertelorism, ptosis, flat midface, thin upper lip, and pointed chin. He also had kyphosis, scoliosis, and finger contractures. The second patient (patient 439) was a 7.5-year-old boy, born of unrelated Dutch parents, with feeding difficulties as a neonate followed by delayed motor, cognitive, and language development with a hoarse voice. He had difficulty regulating emotions and had anxiety. Other features included constipation, short stature, brachydactyly, and dysmorphic features, including upslanting palpebral fissures, blepharophimosis, ptosis, full nasal tip, and pointed chin. Reijnders et al. (2018) reported 38 unrelated individuals and 2 affected mothers with a neurodevelopmental disorder associated with heterozygous variants in the TLK2 gene. Five of the patients had previously been reported by Lelieveld et al. (2016). The majority of the patients had delayed development with motor and language delay and were examined in childhood. Most (72%) had intellectual disability (IQ less than 70), 14% had borderline intellectual disability (IQ 70-85), and 6% had normal IQ (85 to 100). There was a broad range of behavioral abnormalities (present in 68% overall), including autism spectrum disorder, attention deficit-hyperactivity disorder, anxiety, obsessive-compulsive disorder, and social or emotional problems. Neurologic problems included hypotonia (37%), epilepsy (13%), and nonspecific intracranial brain abnormalities (13%). Skeletal abnormalities were observed in some patients, including joint hypermobility (21%), pes planus (21%), toe walking (18%), scoliosis (8%), and hand contractures (8%). Abnormalities of skull shape were seen in 31% of probands, including craniosynostosis in 4 patients. Common dysmorphic features included blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Less common dysmorphic features included pointed and tall chin (42%), epicanthal folds (42%), narrow mouth (32%), high palate (30%), microtia, first degree (29%), posteriorly rotated ears (29%), long face (27%), ptosis (21%), strabismus (26%), asymmetric face (16%), and hypertrichosis (16%). Short stature (37%) and microcephaly (24%) were also observed. Additional features included neonatal feeding difficulties (42%), constipation (55%), diarrhea (8%), recurrent otitis media (24%), eye refraction abnormalities (29%), and hoarse voice (8%). Inheritance The transmission pattern of MRD57 in 2 of the families reported by Reijnders et al. (2018) was consistent with autosomal dominant inheritance. Molecular Genetics In 2 unrelated patients with MRD57, Lelieveld et al. (2016) identified de novo heterozygous mutations in the TLK2 gene (608439.0001 and 608439.0002). The patients were part of a cohort of 820 parent-child trios with intellectual disability who underwent exome sequencing. Functional studies of the variants were not performed, but the mutations were predicted to result in a loss of function and haploinsufficiency. Subsequent addition of data from 4 large previously published family-based sequencing studies identified 3 additional patients with TLK2 mutations. The entire cohort contained 2,104 family trios. In 38 patients and 2 of their mothers with MRD57, Reijnders et al. (2018) identified heterozygous mutations in the TLK2 gene (see, e.g., 608439.0001-608439.0006). Five of the patients had previously been reported by Lelieveld et al. (2016). The vast majority of the mutations reported by Reijnders et al. (2018) occurred de novo, but there were 2 families in which the proband inherited a mutation from an affected mothers. Mutation types included 4 frameshift variants, 10 nonsense variants, 12 splice-site variants, and 9 missense variants. One patient carried a de novo balanced translocation. The mutations occurred throughout the gene. The authors performed RNA analysis of cells derived from 3 patients, which demonstrated that 2 of the mutations were subject to nonsense-mediated mRNA decay (NMD), resulting in haploinsufficiency; the third mutation was a nonsense mutation that escaped NMD, but was predicted to result in a truncated protein and haploinsufficiency. The mutations were found by whole-exome or whole-genome sequencing, and the patients and data were collected from 26 different research institutions in 7 different countries by means of data sharing by collaborators and matchmaker databases. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of patients with loss-of-function variants overlapped with phenotypes of individuals with missense and C-terminal truncated mutations, suggesting that that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature (37%) HEAD & NECK Head \- Microcephaly (24%) Face \- Asymmetric face \- Long face \- Pointed tall chin Ears \- Posteriorly rotated ears \- Otitis media Eyes \- Blepharophimosis \- Telecanthus \- Epicanthal folds \- Upslanting palpebral fissures \- Refraction abnormalities \- Strabismus \- Ptosis Nose \- Prominent nasal bridge \- Broad nasal tip Mouth \- Thin vermilion of the upper lip \- Narrow mouth \- High palate ABDOMEN Gastrointestinal \- Feeding difficulties \- Constipation \- Diarrhea SKELETAL \- Joint hypermobility Skull \- Craniosynostosis (11%) Spine \- Scoliosis \- Kyphosis Hands \- Finger contractures Feet \- Pes planus SKIN, NAILS, & HAIR Hair \- Hypertrichosis MUSCLE, SOFT TISSUES \- Hypotonia NEUROLOGIC Central Nervous System \- Global developmental delay \- Motor delay \- Toe walking \- Intellectual disability, mild to moderate \- Normal cognition (6%) \- Language delay \- Seizures (13%) \- Nonspecific intracranial abnormalities (in some patients) Behavioral Psychiatric Manifestations \- Autism spectrum disorder \- Attention deficit-hyperactivity disorder (ADHD) \- Obsessive-compulsive disorder \- Tantrums \- Anxiety MISCELLANEOUS \- Highly variable phenotype \- Onset in infancy \- De novo mutation (in most patients) Percentages noted above are estimates from Reijnders et al. (2018) MOLECULAR BASIS \- Caused by mutation in the tousled-like kinase 2 gene (TLK2, 608439.0001 ) ▲ Close *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

MENTAL RETARDATION, AUTOSOMAL DOMINANT 57

None

omim

https://www.omim.org/entry/618050

{"omim": ["618050"]}

Schwannomatosis is a disorder characterized by multiple noncancerous (benign) tumors called schwannomas, which are a type of tumor that grows on nerves. Schwannomas develop when Schwann cells, which are specialized cells that normally form an insulating layer around the nerve, grow uncontrollably to form a tumor. The signs and symptoms of schwannomatosis usually appear in early adulthood. The most common symptom is long-lasting (chronic) pain, which can affect any part of the body. In some cases, the pain is felt in areas where there are no known tumors. The pain associated with this condition ranges from mild to severe and can be difficult to manage. Other signs and symptoms that can occur with schwannomatosis depend on the location of the tumors and which nerves are affected. These problems include numbness, weakness, tingling, and headaches. The life expectancy of people with schwannomatosis is normal. Schwannomatosis is usually considered to be a form of neurofibromatosis, which is a group of disorders characterized by the growth of tumors in the nervous system. The other two recognized forms of neurofibromatosis are neurofibromatosis type 1 and neurofibromatosis type 2. The features of schwannomatosis can be very similar to those of neurofibromatosis type 2. However, schwannomatosis almost never includes inner ear tumors called vestibular schwannomas, which are a hallmark of neurofibromatosis type 2. Additional features of the other forms of neurofibromatosis, including the development of other types of tumors, are much less common in schwannomatosis. ## Frequency The incidence of schwannomatosis is unknown, although estimates in several populations have ranged from 1 in 40,000 to 1 in 1.7 million people. Some researchers have suggested that schwannomatosis may be as common as neurofibromatosis type 2, which has an incidence of 1 in 33,000 people worldwide. Schwannomatosis accounts for only a small percentage of all schwannoma tumors. Most schwannomas are isolated, meaning that an individual develops only a single tumor. It is rarer to have multiple schwannomas, as occurs in schwannomatosis. ## Causes Mutations in at least two genes, SMARCB1 and LZTR1, can cause schwannomatosis. The proteins produced from both genes are thought to act as tumor suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in either of these genes may help cells grow and divide without control or order to form a tumor. It appears that mutations in the SMARCB1 or LZTR1 gene alone are not enough to trigger the development of schwannomas. Additional genetic changes (somatic mutations) that are acquired during a person's lifetime and are present only in certain cells may also be required for schwannomas to form. The most common somatic mutations in schwannomas are mutations in the NF2 gene and a loss of chromosome 22 (which is the chromosome on which the SMARCB1, LZTR1, and NF2 genes are found). Some people with schwannomatosis do not have an identified mutation in the SMARCB1 or LZTR1 gene. In these cases, the cause of the disorder is unknown. Researchers suspect that mutations in other as-yet-unidentified genes, most likely on chromosome 22, also contribute to this condition. ### Learn more about the genes associated with Schwannomatosis * LZTR1 * NF2 * SMARCB1 ## Inheritance Pattern Most cases of schwannomatosis are sporadic, which means that they occur in people with no history of the disorder in their family. Some people with sporadic schwannomatosis have mutations in the SMARCB1 or LZTR1 gene, but in others, the cause of the condition is unknown. Studies suggest that 15 to 25 percent of cases of schwannomatosis run in families. These familial cases have an autosomal dominant pattern of inheritance, which means a mutation in one copy of the SMARCB1 or LZTR1 gene in each cell greatly increases the risk of developing schwannomas. However, some people who have an altered gene never develop tumors, which is a situation known as reduced penetrance. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Schwannomatosis

c4048809

medlineplus

https://medlineplus.gov/genetics/condition/schwannomatosis/

{"gard": ["4768"], "omim": ["162091", "615670"], "synonyms": []}

Histidinemia is a rare metabolic disorder characterized by elevated histidine levels in blood, urine, and cerebrospinal fluid, generally with no clinical repercussions. ## Epidemiology Reported prevalence varies widely from 1/8,600 to 1/180,000, probably as a result of differing screening programs. ## Clinical description Histidinemia is defined biochemically as elevated histidine in blood, urine and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and the skin. In most individuals with histidinemia, the condition is clinically silent and considered benign, with no need for treatment or a specific diet. In a small subset of patients with specific events in the neonatal period, such as low oxygen, it has been suggested that histidinemia may contribute to development of intellectual disability, behavioral or learning disorders. Growth is normal in patients with the disorder. Histidinemia is important because in the 1960s and 1970s the condition was unnecessarily added to universal newborn screening before the natural history was fully understood. ## Etiology Histidinemia is caused by impaired conversion of histidine to urocanic acid via the histidase enzyme. Deficiency in this enzyme is related to mutations in the histidine ammonia-lyase HAL gene (12q22-q24.1). ## Diagnostic methods The disease can be diagnosed with blood and urine tests. Nano optical probe samarium tetracycline can be used. The diagnosis can be confirmed by demonstrating the absence or marked reduction of histidase activity in skin or the absence of urocanic acid in skin. ## Genetic counseling Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy. ## Management and treatment Restricting dietary histidine brings the blood histidine level back to normal and eliminates the urinary imidazole metabolites in patients with histidinemia and urocanase deficiency. However, no urgent treatment is required because of the benign nature of this condition. ## Prognosis The life expectancy is not affected. Patients with histidinemia show good prognosis. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Histidinemia

c0220992

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2157

{"gard": ["6661"], "mesh": ["C538320"], "omim": ["235800"], "umls": ["C0220992", "C0268642"], "icd-10": ["E70.8"], "synonyms": ["HAL deficiency", "HIS deficiency", "Histidase deficiency", "Histidine ammonia-lyase deficiency", "Histidinuria", "Hyperhistidinemia"]}

Clear-cell tumor (any with Clear cells) can refer to: * clear-cell sarcoma, including * clear-cell sarcoma of the kidney * clear-cell carcinoma, all/mostly * clear-cell adenocarcinoma Disambiguation page providing links to topics that could be referred to by the same search term This disambiguation page lists articles associated with the title Clear-cell tumor. If an internal link led you here, you may wish to change the link to point directly to the intended article. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Clear-cell tumor

c1265994

wikipedia

https://en.wikipedia.org/wiki/Clear-cell_tumor

{"umls": ["C1265994"], "wikidata": ["Q4000419"]}

Hendra virus infection is a rare viral infection disorder caused by the Hendra virus characterized by onset of flu-like symptoms (fever, myalgia, headaches, lethargy) approximately one week after having been in close contact with bodily fluids of infected horses. Neurological manifestations (e.g. vertigo, confusion, ataxia) and progressive respiratory failure, leading to death, have also been reported. *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Hendra virus infection

c4505487

orphanet

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324632

{"mesh": ["D045464"], "icd-10": ["B33.8"]}

Woolly hair nevus SpecialtyMedical genetics Woolly hair nevus (alternatively spelled "Wooly hair nevus") is a congenital condition in which hair in a circumscribed area of the scalp is kinked or woolly.[1] ## See also[edit] * Woolly hair * Naxos syndrome * Striate palmoplantar keratoderma, woolly hair, and left ventricular dilated cardiomyopathy * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 851. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: Q82.5 (ILDS Q82.550) This Epidermal nevi, neoplasms, cysts article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Woolly hair nevus

c0343114

wikipedia

https://en.wikipedia.org/wiki/Woolly_hair_nevus

{"umls": ["C0343114"], "icd-10": ["Q82.5"], "orphanet": ["79414"], "wikidata": ["Q8033871"]}

Chemotherapy-induced acral erythema Other namesPalmar-plantar erythrodysesthesia, palmoplantar erythrodysesthesia, hand-foot syndrome Pictures of hands on capecitabine SpecialtyDermatology Chemotherapy-induced acral erythema is reddening, swelling, numbness and desquamation (skin sloughing or peeling) on palms of the hands and soles of the feet (and, occasionally, on the knees, elbows, and elsewhere) that can occur after chemotherapy in patients with cancer. Hand-foot syndrome is also rarely seen in sickle-cell disease. These skin changes usually are well demarcated. Acral erythema typically disappears within a few weeks after discontinuation of the offending drug.[1][2] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathogenesis * 4 Diagnosis * 5 Prevention * 6 Treatment * 7 Prognosis * 8 History * 9 References * 10 Further reading * 11 External links ## Signs and symptoms[edit] Foot on capecitabine The symptoms can occur anywhere between days to months after administration of the offending medication, depending on the dose and speed of administration.[3][4] The patient first experiences tingling and/or numbness of the palms and soles. This is followed 2-4 days later by bright redness, which is symmetrical and sharply defined. [5] In severe cases this may be followed by burning pain and swelling, blistering and ulceration, peeling of the skin. [6] Healing occurs without scarring unless there has been skin ulceration or necrosis (skin loss/death). With each subsequent cycle of chemotherapy, the reaction will appear more quickly, be more severe and will take longer to heal.[7] ## Causes[edit] Cabozantinib Acral erythema is a common adverse reaction to cytotoxic chemotherapy drugs, particularly cabozantinib, cytarabine, doxorubicin, and fluorouracil and its prodrug capecitabine.[3] Targeted cancer therapies, especially the tyrosine kinase inhibitors sorafenib and sunitinib, have also been associated with a high incidence of acral erythema. However, acral erythema due to tyrosine kinase inhibitors seems to differ somewhat from acral erythema due to classic chemotherapy drugs.[8] ## Pathogenesis[edit] The cause of Palmar-plantar erythrodysesthesia (PPE) is unknown. Existing hypotheses are based on the fact that only the hands and feet are involved and posit the role of temperature differences, vascular anatomy, differences in the types of cells (rapidly dividing epidermal cells and eccrine glands).[citation needed] In the case of PPE caused by PLD, the following mechanism has been demonstrated: sweat deposits and spreads the drug on the skin surface; then the drug penetrates into the stratum corneum like an external agent; palms and soles have high density of sweat glands, and their stratum corneum is approximately 10 times thicker than the rest of the body, and becomes an efficient long-term reservoir for the penetrating PLD, which was deposited on the skin before.[9] ## Diagnosis[edit] Painful red swelling of the hands and feet in a patient receiving chemotherapy is usually enough to make the diagnosis. The problem can also arise in patients after bone marrow transplants, as the clinical and histologic features of PPE can be similar to cutaneous manifestations of acute (first 3 weeks) graft-versus-host disease. It is important to differentiate PPE, which is benign, from the more dangerous graft-versus-host disease. As time progresses, patients with graft-versus-host disease progress to have other body parts affected, while PPE is limited to hands and feet. Serial biopsies every 3 to 5 days can also be helpful in differentiating the two disorders.[10] ## Prevention[edit] The cooling of hands and feet during chemotherapy may help prevent PPE.[3][11] Support for this and a variety of other approaches to treat or prevent acral erythema comes from small clinical studies, although none has been proven in a randomised controlled clinical trial of sufficient size.[12] Modifying some daily activities to reduce friction and heat exposure to your hands and feet for a period of time following treatment (approximately one week after IV medication, much as possible during the time you are taking oral (by mouth) medication such as capecitabine).[13] * Avoid long exposure of hands and feet to hot water such as washing dishes, long showers, or tub baths. * Short showers in tepid water will reduce exposure of the soles of your feet to the drug. * Dishwashing gloves should not be worn, as the rubber will hold heat against your palms. * Avoid increased pressure on the soles of the feet or palms of hands. * No jogging, aerobics, power walking, jumping - avoid long days of walking. * You should also avoid using garden tools, household tools such as screwdrivers, and other tasks where you are squeezing your hand on a hard surface. * Using knives to chop food may also cause excessive pressure and friction on your palms.[14] ## Treatment[edit] The main treatment for acral erythema is discontinuation of the offending drug, and symptomatic treatment to provide analgesia, lessen edema, and prevent superinfection. However, the treatment for the underlying cancer of the patient must not be neglected. Often, the discontinued drug can be substituted with another cancer drug or cancer treatment.[15][16] Symptomatic treatment can include wound care, elevation, and pain medication. Various emollients (creams) are recommended to keep skin moist. Corticosteroids and pyridoxine have also been used to relieve symptoms.[17] Other studies do not support the conclusion. A number of additional remedies are listed in recent medical literature.[18][19][20][21][22] Among them henna and 10% uridine ointment which went through clinical trial.[23] ## Prognosis[edit] Hand-foot invariably recurs with the resumption of chemotherapy. Long-term chemotherapy may also result in reversible palmoplantar keratoderma. Symptoms resolve 1–2 weeks after cessation of chemotherapy (Apisarnthanarax and Duvic 2003). The range is 1-5 wks, so it has recovered by the time the next cycle is due. Healing occurs without scarring unless there has been skin ulceration or necrosis (skin loss/death). With each subsequent cycle of chemotherapy, the reaction will appear more quickly, be more severe and will take longer to heal.[24] ## History[edit] Hand-foot syndrome was first reported in association with chemotherapy by Zuehlke in 1974.[25] Synonyms for acral erythema (AE) include: hand-foot syndrome, palmar-plantar erythrodysesthesia, peculiar AE, chemotherapy-induced AE, toxic erythema of the palms and soles, palmar-plantar erythema, and Burgdorf's reaction. Common abbreviations are HFS and PPE. ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.:132 2. ^ Rosenbeck L, Kiel PJ (2011). "Images in clinical medicine. Palmar-plantar rash with cytarabine therapy". N. Engl. J. Med. 364 (3): e5. doi:10.1056/NEJMicm1006530. PMID 21247311. 3. ^ a b c Baack BR, Burgdorf WH (1991). "Chemotherapy-induced acral erythema". J. Am. Acad. Dermatol. 24 (3): 457–61. doi:10.1016/0190-9622(91)70073-b. PMID 2061446. 4. ^ Demirçay Z, Gürbüz O, Alpdoğan TB, Yücelten D, Alpdoğan O, Kurtkaya O, Bayik M (1997). "Chemotherapy-induced acral erythema in leukemic patients: a report of 15 cases". Int. J. Dermatol. 36 (8): 593–8. doi:10.1046/j.1365-4362.1997.00040.x. PMID 9329890. 5. ^ https://dermnetnz.org/topics/hand-foot-syndrome/ 6. ^ Apisarnthanarax N, Duvic MM (2003). "Acral Erythema -Holland-Frei Cancer Medicine 6th Edition". NCBI. American Association for Cancer Research. 7. ^ https://dermnetnz.org/topics/hand-foot-syndrome/ 8. ^ Lacouture ME, Reilly LM, Gerami P, Guitart J (2008). "Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib". J. Ann Oncol. 19 (11): 1955–61. doi:10.1093/annonc/mdn389. PMID 18550575. 9. ^ Lademann, Juergen; Martschick, Anja; Kluschke, Franziska; Richter, Heike; Fluhr, Joachim W.; Patzelt, Alexa; Jung, Sora; Chekerov, Radoslav; Darvin, Maxim E.; Haas, Norbert; Sterry, Wolfram; Zastrow, Leonhard; Sehouli, Jalid (2014). "Efficient prevention strategy against the development of a palmar-plantar erythrodysesthesia during chemotherapy". Skin Pharmacology and Physiology. 27 (2): 66–70. doi:10.1159/000351801. ISSN 1660-5535. PMID 23969763. 10. ^ Crider MK, Jansen J, Norins AL, McHale MS (1986). "Chemotherapy-induced acral erythema in patients receiving bone marrow transplantation". Arch Dermatol. 122 (9): 1023–7. doi:10.1001/archderm.122.9.1023. PMID 3527075. 11. ^ Zimmerman GC, Keeling JH, Burris HA, Cook G, Irvin R, Kuhn J, McCollough ML, Von Hoff DD (1995). "Acute cutaneous reactions to docetaxel, a new chemotherapeutic agent". Arch Dermatol. 131 (2): 202–6. doi:10.1001/archderm.1995.01690140086015. PMID 7857119. 12. ^ von Moos, Roger; Thuerlimann, Beat J. K.; Aapro, Matti; Rayson, Daniel; Harrold, Karen; Sehouli, Jalid; Scotte, Florian; Lorusso, Domenica; Dummer, Reinhard; Lacouture, Mario E.; Lademann, Jürgen; Hauschild, Axel (April 2008). "Pegylated liposomal doxorubicin-associated hand-foot syndrome: recommendations of an international panel of experts". European Journal of Cancer. 44 (6): 781–790. doi:10.1016/j.ejca.2008.01.028. ISSN 0959-8049. PMID 18331788. 13. ^ http://chemocare.com/chemotherapy/side-effects/handfoot-syndrome.aspx 14. ^ https://www.breastcancer.org/treatment/side_effects/hand_foot_synd 15. ^ Cutaneous complications of conventional chemotherapy agents. Payne AS, Savarese DMF. In: UpToDate [Textbook of Medicine]. Massachusetts Medical Society, and Wolters Kluwer publishers. 2010. 16. ^ Gressett SM, Stanford BL, Hardwicke F (Sep 2006). "Management of hand-foot syndrome induced by capecitabine". J Oncol Pharm Pract. 12 (3): 131–41. doi:10.1177/1078155206069242. PMID 17022868. 17. ^ Vukelja SJ, Baker WJ, Burris HA, Keeling JH, Von Hoff D (1993). "Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with taxotere". J. Natl. Cancer Inst. 85 (17): 1432–3. doi:10.1093/jnci/85.17.1432. PMID 8102408. 18. ^ Juergen Barth (March 2004). "Letter to the editor - 5-FU induced palmar-plantar erythrodyesthesia – a hospital pharmacy developed "antidot"". Journal of Oncology Pharmacy Practice. 10 (57). 19. ^ Yucel, Idris; Guzin, Gonullu (2008). "Topical henna for capecitabine induced hand-foot syndrome". Investigational New Drugs. 26 (2): 189–192. doi:10.1007/s10637-007-9082-3. ISSN 0167-6997. PMID 17885735. 20. ^ Hartinger, J.; Veselý, P.; Matoušková, E.; Argalacsová, S.; Petruželka, L.; Netíková, I. (2012). "Local treatment of hand-foot syndrome with uridine/thymidine: in vitro appraisal on a human keratinocyte cell line HaCaT". TheScientificWorldJournal. 2012: 421325. doi:10.1100/2012/421325. ISSN 1537-744X. PMC 3417181. PMID 22919318. 21. ^ Hand-Foot Syndrome in cancer patients: concepts, assessment and management of symptoms. 2013. 22. ^ Ilyas, Saher; Wasif, Komal; Saif, Muhammad Wasif (2014). "Topical henna ameliorated capecitabine-induced hand-foot syndrome". Cutaneous and Ocular Toxicology. 33 (3): 253–255. doi:10.3109/15569527.2013.832280. ISSN 1556-9535. PMID 24021017. 23. ^ Irena Netikova; Agnes Petska; Juergen Barth (2009). "Recent clinical studies with uridine cream" (PDF). EJOP. Oncology Pharmacy Practice. 3 (2): 22–23. Archived from the original (PDF) on 2016-03-04. Retrieved 2015-08-26. 24. ^ https://dermnetnz.org/topics/hand-foot-syndrome/ 25. ^ Zuehlke RL (1974). "Erythematous eruption of the palms and soles associated with mitotane therapy". Dermatologica. 148 (2): 90–2. doi:10.1159/000251603. PMID 4276191. ## Further reading[edit] * Farr, Katherina Podlekareva; Safwat, Akmal (2011). "Palmar-Plantar Erythrodysesthesia Associated with Chemotherapy and Its Treatment". Case Reports in Oncology. 4 (1): 229–235. doi:10.1159/000327767. PMC 3085037. PMID 21537373. * Hand-Foot Syndrome or Palmar-Plantar Erythrodysesthesia (1&2) ## External links[edit] Classification D * ICD-10: Y43.1, Y43.3 * ICD-9-CM: 693.0, E933.1 * MeSH: D060831 * DiseasesDB: 34044 * v * t * e Dermatitis and eczema Atopic dermatitis * Besnier's prurigo Seborrheic dermatitis * Pityriasis simplex capillitii * Cradle cap Contact dermatitis (allergic, irritant) * plants: Urushiol-induced contact dermatitis * African blackwood dermatitis * Tulip fingers * other: Abietic acid dermatitis * Diaper rash * Airbag dermatitis * Baboon syndrome * Contact stomatitis * Protein contact dermatitis Eczema * Autoimmune estrogen dermatitis * Autoimmune progesterone dermatitis * Breast eczema * Ear eczema * Eyelid dermatitis * Topical steroid addiction * Hand eczema * Chronic vesiculobullous hand eczema * Hyperkeratotic hand dermatitis * Autosensitization dermatitis/Id reaction * Candidid * Dermatophytid * Molluscum dermatitis * Circumostomy eczema * Dyshidrosis * Juvenile plantar dermatosis * Nummular eczema * Nutritional deficiency eczema * Sulzberger–Garbe syndrome * Xerotic eczema Pruritus/Itch/ Prurigo * Lichen simplex chronicus/Prurigo nodularis * by location: Pruritus ani * Pruritus scroti * Pruritus vulvae * Scalp pruritus * Drug-induced pruritus * Hydroxyethyl starch-induced pruritus * Senile pruritus * Aquagenic pruritus * Aquadynia * Adult blaschkitis * due to liver disease * Biliary pruritus * Cholestatic pruritus * Prion pruritus * Prurigo pigmentosa * Prurigo simplex * Puncta pruritica * Uremic pruritus Other * substances taken internally: Bromoderma * Fixed drug reaction * Nummular dermatitis * Pityriasis alba * Papuloerythroderma of Ofuji * v * t * e Adverse drug reactions Antibiotics * Penicillin drug reaction * Sulfonamide hypersensitivity syndrome * Urticarial erythema multiforme * Adverse effects of fluoroquinolones * Red man syndrome * Jarisch–Herxheimer reaction Hormones * Steroid acne * Steroid folliculitis Chemotherapy * Chemotherapy-induced acral erythema * Chemotherapy-induced hyperpigmentation * Scleroderma-like reaction to taxanes * Hydroxyurea dermopathy * Exudative hyponychial dermatitis Anticoagulants * Anticoagulant-induced skin necrosis * Warfarin necrosis * Vitamin K reaction * Texier's disease Immunologics * Adverse reaction to biologic agents * Leukotriene receptor antagonist-associated Churg–Strauss syndrome * Methotrexate-induced papular eruption * Adverse reaction to cytokines Other drugs * Anticonvulsant hypersensitivity syndrome * Allopurinol hypersensitivity syndrome * Vaccine adverse event * Eczema vaccinatum * Bromoderma * Halogenoderma * Iododerma General Skin and body membranes * Acute generalized exanthematous pustulosis * Bullous drug reaction * Drug-induced acne * Drug-induced angioedema * Drug-related gingival hyperplasia * Drug-induced lichenoid reaction * Drug-induced lupus erythematosus * Drug-induced nail changes * Drug-induced pigmentation * Drug-induced urticaria * Stevens–Johnson syndrome * Injection site reaction * Linear IgA bullous dermatosis * Toxic epidermal necrolysis * HIV disease-related drug reaction * Photosensitive drug reaction Other * Drug-induced pseudolymphoma * Fixed drug reaction * Serum sickness-like reaction *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Chemotherapy-induced acral erythema

c0549410

wikipedia

https://en.wikipedia.org/wiki/Chemotherapy-induced_acral_erythema

{"mesh": ["D060831"], "umls": ["C0549410"], "icd-9": ["693.0"], "icd-10": ["Y43.3", "Y43.1"], "wikidata": ["Q593277"]}

Hypergeusia is a taste disorder where the sense is abnormally heightened.[1][2] It can be associated with a lesion of the posterior fossa and Addison's disease; where a patient will crave for salty and sour taste due to the abnormal loss of ions with urine.[3] ## References[edit] 1. ^ "Definition: hypergeusia from Online Medical Dictionary". 2. ^ "Dorlands Medical Dictionary:hypergeusia".[permanent dead link] 3. ^ Noda S, Hiromatsu K, Umezaki H, Yoneda S (June 1989). "Hypergeusia as the presenting symptom of a posterior fossa lesion". J. Neurol. Neurosurg. Psychiatry. 52 (6): 804–5. doi:10.1136/jnnp.52.6.804-a. PMC 1032046. PMID 2545829. * v * t * e Symptoms and signs relating to perception, emotion and behaviour Cognition * Confusion * Delirium * Psychosis * Delusion * Amnesia * Anterograde amnesia * Retrograde amnesia * Convulsion * Dizziness * Disequilibrium * Presyncope/Lightheadedness * Vertigo Emotion * Anger * Anxiety * Depression * Fear * Paranoia * Hostility * Irritability * Suicidal ideation Behavior * Verbosity * Russell's sign Perception * Sensory processing disorder * Hallucination (Auditory hallucination) * Smell * Anosmia * Hyposmia * Dysosmia * Parosmia * Phantosmia * Hyperosmia * Synesthesia * Taste * Ageusia * Hypogeusia * Dysgeusia * Hypergeusia This medical sign article is a stub. You can help Wikipedia by expanding it. * v * t * e *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[c.]: circa *[AA]: Adrenergic agonist *[AD]: Acetaldehyde dehydrogenase

Hypergeusia

c2609164

wikipedia

https://en.wikipedia.org/wiki/Hypergeusia

{"umls": ["C2609164"], "wikidata": ["Q5958019"]}