TaoMedAI/RareMedData huggingface dataset:
Alpha-thalassemia-myelodysplastic syndrome (ORPHA:231401)
An acquired form of alpha-thalassemia characterized by a myelodysplastic syndrome (MDS) or more rarely a myeloproliferative disease (MPD) associated with hemoglobin H disease (HbH).
Epidemiology
About 80 cases have been identified to date and most involved patients are of northern European descent. Some cases have been reported in patients from Asia and the Mediterranean area.
Clinical description
ATMDS occurs predominantly in males during the 7th decade of life (male-to-female ratio greater than 6:1). The main clinical features include anemia and other signs associated with MDS such as shortness of breath, weakness, tendency to bruise or bleed and an increased susceptibility to infections. It has occasionally been associated with MPD and in these cases, splenomegaly frequently co-occurs. MDS progresses to leukemia in about 25% of cases and HbH is usually no longer detectable at this time.
Etiology
ATMDS is due to acquired somatic mutations in the ATRX gene (Xq21.1). There is also evidence that acquired deletions of chromosome 16p may be causative. These defects result in significant down-regulation of alpha-globin gene expression.
Diagnostic methods
Typical hematological findings show hypochromic microcytic red blood cells and striking anisopoikilocytosis, and the presence of HbH inclusions in a proportion of red blood cells that varies depending on the patients. Cytological and cytogenetic analysis of bone marrow cells is required to confirm the diagnosis and to classify the underlying MDS. Direct sequencing of the ATRX gene in DNA samples from blood or bone marrow usually indicates a mosaicism, identified by a single nucleotide mutation.
Differential diagnosis
Differential diagnoses include other causes of anemia, cytopenia or microcytosis. It is especially important to exclude an inherited form of alpha-thalassemia by molecular analysis of the HBA locus.
Management and treatment
Treatment depends on the underlying MDS. Stem cell transplantation is the only curative treatment but it is rarely feasible. Other treatment options may include hypomethylant (azacitabine) therapy and lenalinomide. Supportive care includes blood transfusions, erythropoietin stimulating agents, growth factors, antibiotics (if infections are present), and iron chelation therapy in those undergoing long term transfusion therapy.
Prognosis
Prognosis depends on the sub-type of MDS according to the International scoring system (ISS). The scoring system takes into account the percentage of marrow blasts, the severity of cytopenia, and cytogenetic analysis of bone marrow cells. Death is usually due to leukemic transformation, infections due to neutropenia, bleeding related to thrombocytopenia and, in some cases, to other co-morbidities such as cardiovascular disease.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Pr Catherine BADENS  - Pr Christian ROSE
ALPI-related inflammatory bowel disease (ORPHA:597887)
A rare genetic gastroenterological disease characterized by severe, refractory intestinal inflammation with mucosal erosions and ulcerations potentially involving the small and large intestine. Epithelioid granulomas are typically absent. Patients present with severe diarrhea, abdominal pain, vomiting, rectal bleeding, and weight loss.
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome (ORPHA:86818)
A rare constitutional hemolytic anemia that is characterised by the association of Alport syndrome, midface hypoplasia, intellectual deficit and elliptocytosis. It has been described in two families. The syndrome is transmitted as an X-linked trait is caused by a contiguous gene deletion in Xq22.3 involving several genes including COL4A5, FACL4 and AMMECR1.
Alveolar soft tissue sarcoma (ORPHA:163699)
A rare soft tissue sarcoma characterized by a slowly growing, painless space-occupying lesion, composed of large, uniform, epithelioid cells arranged in solid nests and/or alveolar structures, separated by thin, sinusoidal vessels. The tumor mostly affects adolescents and young adults. Early metastasis, most commonly to the lung, bones, and brain, is a characteristic feature and relevant prognostic factor, together with age at presentation and tumor size, while histological features have no prognostic significance.
ALys amyloidosis (ORPHA:93561)
A rare, hereditary amyloidosis with primary renal involvement characterized by amyloid deposition in the kidney glomeruli and medulla, gastrointestinal tract, liver, spleen and slow disease progression. Symptoms and signs include nausea, vomiting, dyspepsia, gastritis, gastrointestinal hemorrhage, abdominal pain, hepatic rupture, sicca syndrome, purpura and petechiae, lymphadenopathy and renal dysfunction.
Amaurosis-hypertrichosis syndrome (ORPHA:1021)
A rare, syndromic, inherited retinal disorder characterized by cone-rod type congenital amaurosis, severe retinal dystrophy leading to visual impairment and profound photophobia (without night blindness), and trichomegaly (bushy eyebrows with synophrys, excessive facial and body hair (including marked circumaleolar hypertrichosis). There have been no further descriptions in the literature since 1989.
Amelo-onycho-hypohidrotic syndrome (ORPHA:1028)
A rare ectodermal dysplasia syndrome characterized by the association of hypocalcified and hypoplastic tooth enamel, distal finger and toenail onycholysis with subungueal hyperkeratosis, and functional hypohidrosis. Additional manifestations include seborrheic scalp dermatitis and rough, dry skin. Lacrymal punctae may be occasionally absent. There have been no further descriptions in the literature since 1975.
Ameloblastic carcinoma (ORPHA:314422)
A rare odontogenic tumor characterized by aggressive clinical course and local destruction, occurring in mandible more often than in maxilla. The most common symptom is a rapidly progressing painful swelling, but it may present as a benign cystic lesion or as a large, rapidly growing mass with ulceration, bone resorption and teeth mobility, as well. The tumor may metastasize, most commonly to the cervical lymph nodes and the lungs.
Ameloblastoma (ORPHA:314419)
A rare, benign, slow-growing odontologic tumor located in the mandible, and on occasion the maxilla, characterized by painless, variable-sized jaw swelling, which if left untreated may lead to a grotesque facial appearance. Occasionally, paresthesias, tooth displacement and adjacent root resorption may be associated. Local invasion is frequently observed, but malignant transformation and metastasis are not common.
Amelocerebrohypohidrotic syndrome (ORPHA:1946)
A genetically heterogeneous autosomal recessive syndrome characterized by the triad of amelogenesis imperfect, infantile onset epilepsy, intellectual disability with or without regression and dementia.
Amelogenesis imperfecta (ORPHA:88661)
A rare genetic odontal or periodontal disorder that represents a group of developmental conditions affecting the structure and clinical appearance of the enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body.
Epidemiology
The prevalence varies from 1:700 to 1:14,000, according to the populations studied.
Clinical description
The enamel may be hypoplastic, hypomineralised or both, and affected teeth may be discoloured, sensitive or prone to disintegration. Amelogenesis imperfecta (AI) exists in isolation or associated with other abnormalities as part of a syndrome.
Etiology
In families with an X-linked form, it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity.
Diagnostic methods
Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. At present, genetic diagnosis is only available as a research tool.
Genetic counseling
It may be sporadic or show autosomal dominant, autosomal recessive or sex-linked inheritance.
Management and treatment
The condition presents social and functional problems and leads to discomfort, but it may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. Longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations.

                            Last update: 
                            April 2007


                            - Expert reviewer(s): 
                            Pr Michael ALDRED  - Pr Agnès BLOCH-ZUPAN  - Pr Peter CRAWFORD
American trypanosomiasis (ORPHA:3386)
A tropical disease mainly found in latin America and transmitted by triatomine insects (mostly Triatoma infestans and Rhodnius prolixus and Panstrongylus megistus) harboring the hemoflagellate protozoan parasite Trypanosoma cruzi. The disease is characterized by an acute phase which is either asymptomatic or manifest with fever, inflammation at the inoculation site (inoculation chancre or chagoma), unilateral palpebral edema called the Romaña sign (when the triatomine bite occurs near the eye), enlarged lymph nodes, and splenomegaly. The chronic phase is lifelong and development of chagasic cardiomyopathy (30%; complex arrhythmias, heart failure, and thromboembolic events), digestive (10%; megaoesophagus and megacolon), neurological (10%; stroke, peripheral neuropathy and autonomic dysfunction), or mixed alterations (10%) may be observed. These can all lead to high morbidity and mortality rates.
Aminoacylase 1 deficiency (ORPHA:137754)
An inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms.
Epidemiology
Prevalence is unknown but less than 20 cases have been reported in the literature so far.
Clinical description
Most individuals with ACY1D identified so far are children who underwent selective screening tests for inborn errors of metabolism prompted mainly by delayed psychomotor development or by the occurrence of seizures. However, there is a considerable phenotypic variability between ACY1D individuals.
Etiology
ACY1D is caused by biallelic mutations in the ACY1 gene (3p21.2). ACY1 catalyzes the formation of free amino acids from N-acetylated precursors. The enzyme is strongly expressed in the human brain and is a potential modifier affecting the severity or manifestation of different neurologic diseases.
Diagnostic methods
Diagnosis is made by gas chromatography-mass spectrometry (GC-MS) analysis of urinary organic acids revealing increased levels of N-acetylated amino acids, including methionine, glutamine, alanine, leucine, glycine, valine, and isoleucine derivatives, or by NMR spectroscopy of urine. The diagnosis can be confirmed by identification of mutations in the ACY1 gene and by detection of reduced ACY1 enzyme activity in Epstein-Barr virus (EBV)-transformed lymphoblasts or in fibroblasts.
Genetic counseling
ACY1D is transmitted as an autosomal recessive trait.
Management and treatment
Management is symptomatic only.
Prognosis
Due to the small number of individuals known to have ACY1D and due to the young age of the reported patients, the clinical course cannot be fully predicted and the prognosis is unknown. Characterization of additional patients and long-term follow-up are indicated.

                            Last update: 
                            August 2008


                            - Expert reviewer(s): 
                            Pr Jörn Oliver SASS
Amish lethal microcephaly (ORPHA:99742)
A very rare syndrome characterized by extreme microcephaly and early death, within the first year.
Epidemiology
It has been described only in the Old Order Amish of Lancaster County Pennsylvania. In this population, birth prevalence is about 1/500.
Clinical description
Microcephaly is a microcephalia vera (MV), evident at birth or through 22-week fetal ultrasound. Affected children have high urinary levels of alpha-ketoglutaric acid.
Etiology
All affected infants are homozygous for the same mutation of the SLC25A19 gene on chromosome 17 (17q25.3).
Genetic counseling
The condition follows an autosomal recessive pattern of inheritance.
Prognosis
Prognosis is very poor: the average life span of affected infants is between five and six months.

                            Last update: 
                            December 2010
Amish nemaline myopathy (ORPHA:98902)
A type of nemaline myopathy (NM) only observed in several families of the Amish community.
Clinical description
It has a neonatal onset and patients present with hypotonia associated to contractures, a severe pectus carinatum, and tremor that subsides after 2-3 months of age.
Etiology
TNNT1 (19q13.4) is the causative gene of the Amish NM.
Genetic counseling
Transmission follows an autosomal recessive pattern.
Prognosis
Life expectancy rarely exceeds 2 years as a consequence of severe respiratory insufficiency.

                            Last update: 
                            October 2010


                            - Expert reviewer(s): 
                            Dr Monique RYAN
Amniotic band syndrome (ORPHA:295000)
Constriction rings syndrome is a congenital limb malformation disorder with an extremely variable clinical presentation characterized by the presence of partial to complete, congenital, fibrous, circumferential, constriction bands/rings on any part of the body, although a particular predilection for the upper or lower extremities is seen. Phenotypes range from only a mild skin indentation to complete amputation of parts of the fetus (e.g. digits, distal limb). Compression from the rings may lead to edema, skeletal anomalies (e.g. fractures, foot deformities) and, infrequently, neural compromise.
Amoebiasis due to Entamoeba histolytica (ORPHA:67)
A parasitic disease caused by the protozoa, Entamoeba histolytica, mainly occurring in tropical regions after the ingestion of an amoebic cyst, and resulting in clinical manifestations that may range from an asymptomatic state to amoebic colitis (violent abdominal pain, a painful contracted feeling around the anal sphincter, blood and mucus in the stools but without the presence of fever), or amoebic liver abscesses (fever, chills, abdominal pain, weight loss, hepatomegaly) that can be fatal if not immediately treated. Extraintestinal involvement elsewhere (i.e. thoracic, hepatic) is extremely rare.
Amoebiasis due to free-living amoebae (ORPHA:68)
A rare parasitic disease caused by free-living amoebae belonging to the Acanthamoeba, Naegleria and Balamuthia genera, that are able to survive in an autonomous state in all natural environments and can also parasitize humans. In immunosuppressed individuals Acanthamoeba genus contamination leads to granulomatous amoebic encephalitis (also reported in association with species of the Balamuthia genus) together with other problems including cardiac, cutaneous and pulmonary manifestations, all of which influence the prognosis. In immunocompetent individuals, the Naegleria fowleri species is responsible for primary amoebic meningoencephalitis, the evolution of which is rapidly fatal.
Amoebic keratitis (ORPHA:67043)
A rare corneal infection due to the protozoan Acanthamoeba that generally occurs in contact lens wearers and that is characterized by severe ocular pain, blepharospasm, photophobia, eye tearing, blurred vision and foreign body sensation. It can lead to impaired visual acuity if not treated promptly.
Amyloidosis cutis dyschromia (ORPHA:319635)
A rare primary cutaneous amyloidosis characterized by macular or reticulate hyperpigmentation with symmetrically distributed guttate hypo- and hyperpigmented lesions which progress gradually over the years to involve almost the entire body (with relative sparing of the face, hands, feet and neck). Patients are usually asymptomatic, however mild pruritus may be associated. Amyloid deposition in the papillary dermis is observed on skin biopsy. Systemic amyloidosis is not present and association with generalized morphea, atypical Parkinsonism, spasticity, motor weakness or colon carcinoma is rare.
Amyotrophic lateral sclerosis type 4 (ORPHA:357043)
A rare, genetic motor neuron disease characterized by late childhood- or adolescent-onset of slowly progressive, severe, distal limb muscle weakness and wasting, in association with pyramidal signs, normal sensation, and absence of bulbar involvement, leading to degeneration of motor neurons in the brain and spinal cord.
Amyotrophic lateral sclerosis (ORPHA:803)
A neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.
Epidemiology
Incidence (average around 1/50,000 per year) and prevalence (average around 1/20,000) are relatively uniform in Western countries, although foci of higher frequency have been reported in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male preponderance (male to female ratio of around 1.5:1).
Clinical description
Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, in which onset of symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solids or liquids. Limb symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1-2 years. Paralysis is progressive and leads to death due to respiratory failure within 2-3 years for bulbar onset cases and 3-5 years for limb onset ALS cases.
Etiology
Most ALS cases are sporadic but 5-10% of cases are familial, and of these 20% involve a mutation of the SOD1 gene (21q22.11), about 2-5% involve mutations of the TARDBP gene (1p36.22) encoding the TAR DNA-binding protein 43 (TDP-43) and 1-2% involve mutations of the VCP gene (9p13.3) coding for the Valosin Containing Protein. Two percent of apparently sporadic cases involve SOD1 mutations, and TARDBP mutations have also been identified in sporadic cases.
Diagnostic methods
The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. multifocal motor neuropathy, Kennedy's disease (seethese terms) and cervical spondylotic myelopathy) by appropriate investigations. The pathological hallmarks comprise loss of motor neurons with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurons and TDP-43 immunoreactive inclusions in degenerating lower motor neurons. Signs of upper motor neuron and lower motor neuron damage not explained by any other disease process are suggestive of ALS.
Management and treatment
The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Pr Nigel LEIGH  - Dr Lokesh WIJESEKERA
Anal fistula (ORPHA:228113)
A rare intestinal condition characterized by an abnormal communication between the lower rectum and the perianal skin, which usually develops after an acute perianal abscess. A fistulous traject may be established on either side of the anus (never in the midline) and mucous or fecal discharge can appear. The skin around the external orifice can be irritated. Males are more often affected than females.
Anaplastic astrocytoma (ORPHA:251589)
A rare, high-grade, malignant glial tumor, histologically characterized by abundance of pleomorphic astrocytes and multiple mitotic figures, often associated with diffuse infiltration of the surrounding tissue, considerable edema and mass effect and involvement of the contralateral brain. Depending on the primary localization of the tumor, patients can present with signs of raised intracranial pressure (headache, vomiting, papilledema), seizures, progressive neurological deficits, and/or behavioral changes. The tumor is most commonly localized in the frontal and temporal lobes, brain stem and spinal cord.
Anaplastic ependymoma (ORPHA:251646)
A rare, malignant type of ependymoma that most often arises in the supratentorial region of the brain of children and young adults and that manifests with variable symptoms including headaches, nausea, vision impairment, memory loss and difficulty walking.
Anaplastic ganglioglioma (ORPHA:251957)
A rare mixed neuronal-glial tumor characterized by a mostly supratentorial space-occupying lesion often involving the temporal lobe, although it may occur anywhere in the central nervous system. The tumor shows anaplastic features in its glial component and is considered WHO grade III, which may, albeit inconsistently, indicate more aggressive behavior and less favorable prognosis. Clinical symptoms vary according to the location, the most common manifestation being seizures.
Anaplastic oligoastrocytoma (ORPHA:251663)
A rare and aggressive glial tumor of the central nervous system, that usually presents in adults with seizures, is most often located in the cerebral hemispheres and that is associated with a very poor prognosis.
Anaplastic oligodendroglioma (ORPHA:251630)
A rare glial tumor characterized by a grade III oligodendroglial tumour with focal or diffuse anaplastic features. It typically occurs in the supratentorial white matter. Histologically, the cells are enlarged and epithelioid with pleomorphic and increased size nuclei, a vesicular chromatin pattern and prominent nucleoli. Most patients present with seizures.
Anaplastic thyroid carcinoma (ORPHA:142)
A disorder that represents the ultimate dedifferentiation step of thyroid tumorigenesis and is one of the most severe cancers in humans.
Epidemiology
It accounts for less than 2% of thyroid cancers and affects older patients in their sixth to eighth decade.
Clinical description
Usual clinical presentation is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. Cervical lymph nodes enlargement and distant metastases occur frequently.
Diagnostic methods
Though cytological results obtained by fine needle aspiration may be suggestive of diagnosis, tissue biopsy for immunohistochemichal study can be necessary to exclude lymphoma and to validate aggressive therapies.
Management and treatment
Patients developing anaplastic thyroid cancer must be referred urgently in cancer centers to plan multimodality therapeutic approach depending on their performance status. The treatment regimen combines surgery when feasible, hyperfractionated and accelerated external beam radiotherapy and doxorubicin based chemotherapy. Such treatment can provide control of locoregional disease but does not impact on overall survival in patients with distant metastases. Therapeutic research is investigating redifferenciation strategies and targeted therapies to inhibit EGF receptors and neoplastic angiogenesis. Primary prevention of this lethal disease may consist of adequate treatment of differentiated thyroid cancers and goiters in the elderly.
Prognosis
The prognosis is dismal with a mean survival of four to nine months after diagnosis. Long survivors are patients with emerging disease presenting a resectable tumor and receiving adjuvant radiotherapy and/or chemotherapy.

                            Last update: 
                            April 2008


                            - Expert reviewer(s): 
                            Dr Christine DO CAO  - Pr Jean-Louis WEMEAU