TaoMedAI/RareMedData huggingface dataset:
Hirschsprung disease-ganglioneuroblastoma syndrome (ORPHA:2151)
A rare, genetic, developmental defect during embryogenesis syndrome characterized by total or partial colonic aganglionosis associated with peripheral, usually multifocal, neuroblastic tumors (ganglioneuroblastoma, neuroblastoma, ganglioneuroma). Congenital central hypoventilation syndrome, with variable severity of respiratory compromise, cardiovascular and ophthalmologic symptoms, consistent with autonomic nervous system dysfunction, is occasionally associated.
Hirschsprung disease-nail hypoplasia-dysmorphism syndrome (ORPHA:2153)
Hirschsprung disease-nail hypoplasia-dysmorphism syndrome is a fatal malformative disorder that is characterized by Hirschsprung disease, hypoplastic nails, distal limb hypoplasia and minor craniofacial dysmorphic features (flat facies, upward slanting palpebral fissures, narrow philtrum, narrow, high arched palate, micrognathia, low set ears with abnormal helices). Hydronephrosis has also been reported. There have been no further descriptions in the literature since 1988.
Hirschsprung disease-type D brachydactyly syndrome (ORPHA:2150)
Hirschsprung disease-type D brachydactyly syndrome is characterized by Hirschsprung disease and absence or hypoplasia of the nails and distal phalanges of the thumbs and great toes (type D brachydactyly). It has been described in four males from one family (two brothers and two maternal uncles). Transmission appears to be X-linked recessive but autosomal dominant inheritance with incomplete penetrance in females can not be ruled out.
His bundle tachycardia (ORPHA:3283)
His bundle tachycardia is a very rare congenital genetic tachyarrhythmia characterized by incessant tachycardia and high morbidity and mortality.
Histidinemia (ORPHA:2157)
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.

                            Last update: 
                            May 2019


                            - Expert reviewer(s): 
                            Dr Jeffrey BROSCO
Histidinuria-renal tubular defect syndrome (ORPHA:2158)
A rare disorder of histidine metabolism characterized by histidinuria without histidinemia due to impaired intestinal and renal tubular absorption of histidine. Developmental delay, intellectual disability, seizures, and mild dysmorphic features have been reported in association. There have been no further descriptions in the literature since 1992.
Histiocytic sarcoma (ORPHA:86896)
A rare histiocytic tumor characterized by a malignant proliferation of cells showing morphological and immunophenotypic features of mature tissue histiocytes. Most cases occur in extranodal sites, most commonly the intestinal tract, skin, and soft tissue. Patients may present with a solitary mass, lymphadenopathy, a skin rash or numerous tumors on the trunk and extremities, lytic bone lesions, hepatosplenomegaly with pancytopenia, intestinal obstruction, and/or systemic symptoms. The neoplasm is aggressive with typically poor therapy response.
Histoplasmosis (ORPHA:390)
A rare mycosis characterized by granulomatous inflammation primarily of the lung after inhalation of spores of Histoplasma capsulatum. The severity of clinical disease depends on the immune status of the individual and the size of the inoculum. In immunocompetent persons, the infection usually takes a self-limiting and asymptomatic or relatively mild, flu-like course. In immunocompromised patients, it can become progressive and disseminated, involving multiple organs and presenting with fever, pneumonia, hepatosplenomegaly, skin infiltrates, and endocarditis, among others.
HIV-associated cancer (ORPHA:443291)
A rare neoplastic disease characterized by occurrence in association with human immunodeficiency virus (HIV) infection. Kaposi sarcoma, aggressive B-cell lymphomas, and invasive cervical cancer are considered AIDS-defining cancers, while a variety of other cancers are known to be related to HIV, including Hodgkin lymphoma, hepatocellular carcinoma, and lung, anal, oral cavity and oropharyngeal, vulvar, and penile cancer. The majority of cancers in AIDS patients are associated with co-infection with oncogenic viruses, such as Epstein-Barr virus, human herpesvirus 8, and human papillomavirus.
HJV or HAMP-related hemochromatosis (ORPHA:79230)
An early-onset and most severe form of rare hemochromatosis characterized by the usual features of hemochromatosis accompanied by cardiomyopathy and hypogonadism.
Epidemiology
Less than 100 reported cases were reported with a broad geographical distribution. Both sexes are equally affected.
Clinical description
Age of onset is usually less than 30 years. This juvenile form of hemochromatosis has the classical features of symptomatic HC but is also characterized by severe cardiomyopathy and hypogonadism. Arthropathy, hepatic fibrosis, glucose intolerance, and increased skin pigmentation are frequent. Biochemical abnormalities include elevated serum iron, transferrin saturation and ferritin.
Etiology
Two types of the disease have been described, both being transmitted in an autosomal recessive way. The most frequent form is caused by mutations in the hemojuvelin (HJV) gene on chromosome 1 and the second form is caused by mutations in the hepcidin (HAMP) gene on chromosome 19. These mutations result in complete or major hepcidin deficiency, thus increasing drastically duodenal iron absorption and iron release from the spleen.
Diagnostic methods
Diagnosis is based on biochemical testing for serum transferrin saturation (>90%), serum ferritin concentration (often >2000 microg/L), and on magnetic resonance imaging (MRI) for quantifying visceral (especially hepatic and cardiac) iron overload. Molecular genetic blood testing allows, in most cases, to confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes TFR2-related hemochromatosis and post-transfusional iron overload in the case of hematological diseases such as thalassemia major, sickle cell disease, and other rare anemias.
Genetic counseling
Genetic counseling should be offered to first-degree relatives of patients with genetically confirmed HJV or HAMP-related hemochromatosis. Particular focus should be given to siblings as they are at the highest risk (25%).
Management and treatment
Intensive phlebotomies, sometimes combined with iron chelation therapy, form the basis of treatment.
Prognosis
Complications like heart failure are often fatal. Early and intensive iron depletive therapy can significantly improve an otherwise devastating prognosis.

                            Last update: 
                            August 2023


                            - Expert reviewer(s): 
                            Pr Graça PORTO | EuroBloodNet*


                                * European Reference Network
HNRNPDL-related limb-girdle muscular dystrophy D3 (ORPHA:55596)
A rare, mild subtype of autosomal dominant limb-girdle muscular dystrophy characterized by a typically adult onset of mild, progressive, proximal weakness of pelvic and shoulder girdle muscles and progressive, permanent finger and toes flexion limitation without flexion contractures. Normal to highly elevated creatine kinase serum levels are observed.
Hodgkin lymphoma (ORPHA:98293)
Hodgkin lymphoma (HL) is a heterogeneous group of malignant lymphoid neoplasms of B-cell origin characterized histologically by the presence of Hodgkin and Reed-Sternberg (HRS) cells in the vast majority of cases.
Epidemiology
HL is an uncommon cancer with an incidence of about 1/40,000 in North America and Europe. There are about 8500 new cases reported in the U.S. each year.
Clinical description
HL is comprised of 2 major forms: classical Hodgkin lymphoma (CHL; see this term), seen in 95% of all HL cases, and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL; see this term), seen in only 5% of all HL cases. Disease onset occurs most frequently in young adults (age 15-35) followed by older adults (over the age of 55) and usually begins with the painless swelling of a lymph node in the upper body. Disease can spread to multiple lymph node regions or lymphoid structures and associated systemic symptoms (weight loss > 10% of baseline, fevers, night sweats) are observed in about 20% of patients.
Etiology
The exact cause is unknown but immunological, genetic and environmental factors are thought to be involved.
Management and treatment
Treatment with radiotherapy and systemic chemotherapy leads to a very good prognosis. Follow-up physical exams, blood tests and x-rays are needed to check for recurrence and check for any long-term side effects of the toxic treatments. Possible long-term side effects include secondary cancers, infertility, reduced immunity, thyroid problems, heart disease and stroke.
Prognosis
The international prognostic score (IPS) is a score given based on the presence of 7 risk factors (male sex, >45 years of age, stage 4 disease, serum albumin <4g/dl, hemoglobin <10.5 g/l, lymphocytopenia and WBC count >15,000/mm3) at the time of diagnosis. The more factors present, the less favorable the prognosis. The cure rates are 90% for early-stage HL and 70% for advance stage HL.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Joseph CONNORS
Holmes-Adie syndrome (ORPHA:454718)
A rare ophthalmic disorder characterized by the unilateral or bilateral occurrence of a tonic pupil (showing sectorial denervation of the sphincter pupillae, so that the pupil constricts poorly to light, while the response to near is present but abnormally prolonged), in association with the absence of deep tendon reflexes. In some patients, patchy hypo- or anhidrosis may also be present (a variant known as Ross syndrome). The condition typically occurs in young adults, with a female preponderance.
Holoprosencephaly-caudal dysgenesis syndrome (ORPHA:2165)
Holoprosencephaly-caudal dysgenesis syndrome is a central nervous system malformation syndrome characterized by holoprosencephaly with microcephaly, abnormal eye morphology (hypotelorism, cyclopia, exophthalmos), nasal anomalies (single nostril or absent nose), and cleft lip/palate, combined with signs of caudal regression (sacral agenesis, sirenomelia with absent external genitalia).
Holoprosencephaly-craniosynostosis syndrome (ORPHA:2163)
Holoprosencephaly-craniosynostosis syndrome is a rare developmental defect during embryogenesis syndrome characterized by the association of primary craniosynostosis (usually involving the coronal and metopic sutures) with holoprosencephaly (ranging from alobar to, most commonly, semilobar) and various skeletal anomalies (typically, hand and feet anomalies including fifth digit clinodactyly, hypoplastic phalanges and cone-shaped epiphyses, small vertebral bodies, scoliosis, coxa valga and/or flexion deformities of hips). Craniofacial asymmetry, microcephaly, brachy/plagiocephaly, short stature and psychomotor delay are additional common features.
Holoprosencephaly-postaxial polydactyly syndrome (ORPHA:2166)
Holoprosencephaly-postaxial polydactyly syndrome associates, in chromosomally normal neonates, holoprosencephaly, severe facial dysmorphism, postaxial polydactyly and other congenital abnormalities, suggestive of trisomy 13 (see this term).
Epidemiology
Incidence is unknown.
Clinical description
Dysmorphic features include hypotelorism, severe eye anomalies such as microphtalmia or anophtalmia, premaxillary region aplasia and cleft lip and palate. Congenital cardiac anomalies are common.
Antenatal diagnosis
Antenatal diagnosis is possible by ultrasonographic monitoring.
Genetic counseling
The condition seems to be inherited as an autosomal recessive trait.
Prognosis
Prognosis is poor.

                            Last update: 
                            January 2010
Holoprosencephaly-radial heart renal anomalies syndrome (ORPHA:3186)
A rare multiple congenital anomalies syndrome characterised by holoprosencephaly, predominantly radial limb deficiency (absent thumbs, phocomelia), heart defects, kidney malformations and absence of gallbladder. Variable manifestations include vertebral anomalies, cleft lip/palate, microphthalmia, absent nose, dysplastic ears, hearing loss, colobomas of the iris and retina and/or bifid uvula.
Holzgreve syndrome (ORPHA:2167)
Holzgreve syndrome is an extremely rare, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by renal agenesis with Potter sequence, cleft lip/palate, oral synechiae, cardiac defects, and skeletal abnormalities including postaxial polydactyly. Intestinal nonfixation and intrauterine growth restriction are also associated. There have been no further descriptions in the literature since 1988.
Homocystinuria due to methylene tetrahydrofolate reductase deficiency (ORPHA:395)
Homocystinuria due to methylene tetrahydrofolate reductase (MTHFR) deficiency is a metabolic disorder characterised by neurological manifestations.
Epidemiology
The prevalence is unknown.
Clinical description
Onset usually occurs during the first year of life with severe neurological signs, recurrent apnoea, microcephaly and convulsions. There is no megaloblastic anaemia. There are some forms with onset during childhood, adolescence, or adulthood beginning with mental regression, ataxia, and, most often, common psychiatric disorders of the schizophrenic type that may be linked to cerebrovascular accidents. Other symptoms such as subacute degeneration of the spinal chord have been reported.
Etiology
It is caused by mutations in the MTHFR gene (1p36.3). MTHFR deficiency results in abnormal intracellular folic acid metabolism and prevents reduction of 5-10 methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for the remethylation of homocysteine into methionine. As a result, the disorder leads to methyltetrahydrofolate deficiency and consequently to homocystinuria and hypomethioninemia.
Diagnostic methods
Diagnosis may be suspected after analysis of amino acids by chromatography and measurements of total plasma homocysteine levels revealing highly elevated values of >100 micromol/L. Other biological findings include low levels of methyltetrahydrofolate in both the plasma and cerebrospinal fluid. Diagnosis is confirmed by measuring enzyme activity in lymphocytes or fibroblasts.
Differential diagnosis
The differential diagnosis should include other homocysteine remethylation disorders.
Antenatal diagnosis
Prenatal diagnosis is feasible through molecular or enzymatic analysis.
Genetic counseling
The disorder is transmitted as an autosomal recessive trait.
Management and treatment
Treatment of severe deficiency revolves around the administration of high-dose betaine, in combination with methionine, pyridoxine, vitamin B12 and folic or folinic acid supplements.
Prognosis
The prognosis is variable.

                            Last update: 
                            January 2008


                            - Expert reviewer(s): 
                            Pr Pascale DE LONLAY
Horizontal gaze palsy with progressive scoliosis (ORPHA:2744)
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital autosomal recessive disease, presenting in children and adolescents, and characterized by progressive scoliosis along with the absence of conjugate horizontal eye movements and associated with failure of the somatosensory and corticospinal neuronal tracts to decussate in the medulla.
Hot water reflex epilepsy (ORPHA:166412)
Hot water reflex epilepsy is a rare neurologic disease characterized by the onset of generalized or focal seizures following immersion of the head in hot water, or with hot water being poured over the head. Primary generalized tonic-clonic seizures have been reported in rare cases.
House allergic alveolitis (ORPHA:99907)
House allergic alveolitis is a hypersensitivity pneumonitis (see this term) resulting from the inhalation of an antigen to which an individual has been previously sensitized in his/her domestic environment. House allergic alveolitis encompasses summer hypersensitivity pneumonitis, humidifier-induced lung diseases, hot tub lung and legionellosis (see this term).
Hoyeraal-Hreidarsson syndrome (ORPHA:3322)
A rare X-linked syndromic intellectual disability considered to be a severe variant of dyskeratosis congenita characterized by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, progressive combined immune deficiency and aplastic anemia.
Epidemiology
Hoyeraal-Hreidarsson syndrome (HHS) prevalence is unknown. The syndrome may be underdiagnosed due to high mortality rates.
Clinical description
The disease generally presents in early childhood and primarily affects males. Growth retardation is usually of prenatal onset. Other clinical manifestations include microcephaly, mucocutaneous lesions (hyperpigmentation, nail dystrophy, premalignant leukoplakia affecting oral and gastrointestinal mucosa), early onset bone marrow failure, immunodeficiency and pancytopenia. Cancer predisposition is also reported.
Etiology
HSS is caused by mutations in the DKC1 gene (Xq28), encoding the nucleolar protein dyskerin which interacts with the human telomerase RNA complex. Mutations in other genes (TERT, RTEL1 or TINF2, ACD, PARN) involved in telomere maintenance may be associated with this disorder.
Diagnostic methods
The disorder diagnosis is based on neuroimaging. Molecular genetic testing is needed to confirm diagnosis.
Differential diagnosis
Differential diagnoses include dyskeratosis congenita, Revesz-Debuse syndrome, Pseudo-TORCH syndrome, Fanconi anemia and Nijmegen breakage syndrome.
Antenatal diagnosis
Intrauterine growth failure and cerebellar hypoplasia can be detected by prenatal imaging (ultrasounds, MRI). If the familial mutation is known, prenatal genetic testing can be proposed.
Genetic counseling
HHS follows an X-linked recessive pattern of inheritance. The disorder is very rarely inherited as an autosomal recessive form.
Management and treatment
The aplastic anemia and immunodeficiency can be treated by bone marrow transplantation. Supportive treatment for gastrointestinal complications and infections is required.
Prognosis
The prognosis is poor as the disease follows a very severe course and premature death in childhood can occur due to bone marrow failure, but survival into adulthood is possible.

                            Last update: 
                            August 2019


                            - Expert reviewer(s): 
                            Pr Eugen BOLTSHAUSER
HSD10 disease, infantile type (ORPHA:391428)
A clinical subtype of HSD10 disease, a rare neurometabolic disorder. Affected boys may show lethargy, poor feeding and evidence of mitochondrial dysfunction in the newborn period, with subsequent mild developmental delay and abnormal muscle tone. Hallmark of the disease is progressive neurodegeneration and cardiomyopathy, which usually manifests between ages 6 months and 2 years with developmental regression, progressive visual and hearing loss, epilepsy and other neurological symptoms, and severe cardiomyopathy. Laboratory investigations show signs of mitochondrial dysfunction, and increased urinary excretion of specific isoleucine metabolites. The disease is often fatal around 2-4 years of age.
HSD10 disease, neonatal type (ORPHA:391457)
HSD10 disease, neonatal type is the most severe form of HSD10 disease, a rare neurometabolic disorder. It is characterized by severe metabolic/lactic acidosis in the neonatal period, little psychomotor development, seizures and severe progressive hypertrophic cardiomyopathy. Hepatic involvement and coagulopathy are rare. The disease is fatal within the first months of life.
HTRA1-related autosomal dominant cerebral small vessel disease (ORPHA:482077)
A rare genetic cerebral small vessel disease characterized by subcortical ischemic events associated with cognitive decline and gait disturbance with an age of onset typically in the sixth or seventh decade of life. Imaging reveals white matter hyperintensities, status cribrosus, lacunar infarcts, and sometimes microbleeds. Extra-neurological manifestations are absent.