TaoMedAI/RareMedData huggingface dataset:
Hepatoerythropoietic porphyria (ORPHA:95159)
A rare form of hepatic porphyria characterized by bullous photodermatosis.
Epidemiology
Fewer than a hundred cases of hepato-erythropoietic porphyria (HEP) have been described worldwide.
Clinical description
The disease begins in childhood. The main clinical signs include skin fragility, and sometimes erosive or even mutilating bullous skin lesions on sun-exposed surfaces (hands, face). Anemia and splenomegaly may be present. At bone level, delayed metacarpophalangeal growth is usually present. Hepatoerythropoietic porphyria corresponds to homozygous or heterozygous compound cases of porphyria cutanea tarda.
Etiology
The disease is due to a deficiency of uroporphyrinogen decarboxylase (UROD; the fifth enzyme in the heme biosynthesis pathway) resulting from a mutation in the UROD gene (NM_000374.5), which leads to an accumulation of porphyrins mostly in the liver. At least 30 different mutations have been described in the UROD gene, including one predominant substitution: G281D.
Diagnostic methods
Diagnosis is based on evidence of porphyrin accumulation in urine and stool with a characteristic chromatographic profile, and very high porphyrin concentrations in plasma and erythrocytes. The presence of a major (< 10%) UROD deficiency in red blood cells confirms the diagnosis. Skin biopsy is not very informative and is not recommended.
Differential diagnosis
Günther's disease is the main differential diagnosis.
Antenatal diagnosis
Antenatal diagnosis is theoretically possible, but is not proposed.
Genetic counseling
Transmission pattern is autosomal recessive. Genetic counseling should be offered to affected families to identify individuals likely to develop or transmit the disease. Genetic counselling should be offered to at-risk couples (both individuals are carriers of a heterozygous pathogenic variant) informing them that there is a 25 % risk of having an affected child at each pregnancy.
Management and treatment
Care and support mainly involves protecting the skin against light, and blood transfusions in case of anemia. Treatment with hydroxyurea and splenectomy are rarely necessary. Chloroquine and phlebotomy are of limited effectiveness in the treatment of hepato-erythropoietic porphyria.
Prognosis
The long-term prognosis is good.

                            Last update: 
                            March 2024


                            - Expert reviewer(s): 
                            Dr Neila TALBI | MetabERN*


                                * European Reference Network
Hepatoportal sclerosis (ORPHA:64743)
A form of portosinusoidal vascular disease characterized histologically by varying degrees of phlebosclerosis, primarily involving the small and medium branches of the portal vein with heterogeneous distribution, in the absence of cirrhosis.
Hepatosplenic T-cell lymphoma (ORPHA:86882)
A rare T-cell non-Hodgkin lymphoma characterized by a proliferation of cytotoxic T-cells, usually gamma delta T-cells, with involvement of the liver and spleen, but without involvement of lymph nodes. The bone marrow is consistently affected. Patients typically present during adolescence or young adulthood with hepatosplenomegaly, pancytopenia, and systemic symptoms. Peripheral blood involvement may develop later in the disease course. There is a clear male preponderance. The disease often occurs in the context of long-term immunosuppression. The course is aggressive with poor therapy response.
Hereditary acrokeratotic poikiloderma (ORPHA:2907)
A rare hereditary poikiloderma characterized by infantile onset of vesicopustule formation on hands and feet and widespread eczematoid dermatitis (both spontaneously resolving during childhood), as well as gradually developing diffuse poikiloderma with striate and reticulate atrophy (excluding the face, scalp, and ears), and development of keratotic papules on hands, feet, elbows, and knees, beginning in early childhood. There have been no further descriptions in the literature since 1981.
Hereditary amyloidosis with primary renal involvement (ORPHA:85450)
A group of rare renal diseases, characterized by amyloid fibril deposition of apolipoprotein A-I or A-II (AApoAI or AApoAII amyloidosis), lysozyme (ALys amyloidosis) or fibrinogen A-alpha chain (AFib amyloidosis) in one or several organs. Renal involvement leading to chronic renal disease and renal failure is a common sign. Additional manifestations depend on the organ involved and the type of amyloid fibrils deposited.
Hereditary angioedema type 1 (ORPHA:100050)
A form of hereditary angioedema characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.
Epidemiology
Prevalence is unknown but HAE type 1 is the most common form of HAE accounting for 85% of the cases and is seen equally in males and females.
Clinical description
Like HAE 2 and 3 (see these terms), it occurs generally in childhood with symptoms becoming more severe in adolescence. Precipitating factors of HAE 1 thought to trigger attacks include: trauma, anxiety, puberty, infection, alcohol consumption, exercise and stress.
Etiology
It is caused by a missence mutation in the SERPING1 gene encoding the C1 inhibitor (C1-INH). These mutations cause C1-INH levels to decrease leading to an increase in bradykinin formation.
Management and treatment
Treatment usually consists of intravenous C1 inhibitor concentrate or subcutaneous administration of the orphan drug icatibant (bradykinin receptor antagonist). Prophylaxis with danazol is often given before surgical procedures.

                            Last update: 
                            August 2011


                            - Expert reviewer(s): 
                            Pr Laurence BOUILLET
Hereditary angioedema type 2 (ORPHA:100051)
Hereditary angioedema type 2 (HAE 2) is a form of hereditary angioedema (see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.
Epidemiology
Prevalence is unknown. HAE 2 is the less common form of HAE, accounting for 15% of HAE cases and is seen equally in men and women.
Clinical description
Like HAE 1 and 3 (see these terms) it occurs generally in childhood with symptoms becoming more severe in adolescence. Precipitating factors of HAE 2 thought to trigger attacks include: trauma, anxiety, puberty, infection, alcohol consumption, exercise and stress.
Etiology
It is caused by deletions, frameshift or splice mutations in the SERPING1 gene encoding the C1 inhibitor (C1-INH). These mutations cause a decrease in C1-INH activity (while C1 inhibitor serum levels remain normal) leading to an increase in bradykinin formation.
Management and treatment
Treatment usually consists of intravenous C1 inhibitor concentrate or subcutaneous administration of the orphan drug icatibant (bradykinin receptor antagonist). Prophylaxis with danazol is often given before surgical procedures.

                            Last update: 
                            August 2011


                            - Expert reviewer(s): 
                            Pr Laurence BOUILLET
Hereditary angioedema with C1Inh deficiency (ORPHA:528623)
A rare hereditary angioedema characterized by potentially life-threatening episodes of subcutaneous and/or submucosal edema without urticaria, associated with C1 esterase inhibitor (C1-INH) deficiency. Hereditary angioedema (HAE) type 1 is caused by quantitative, HAE type 2 by qualitative defects of C1-INH. The two subtypes are clinically indistinguishable. Patients may present at any age (but most commonly in childhood) with recurrent attacks of nonpitting edema of the skin, severe abdominal symptoms such as pain and swelling, and/or respiratory distress due to upper respiratory airways involvement. Genital, bladder, muscle, or joint swelling may occur in some cases.
Hereditary angioedema with normal C1Inh (ORPHA:528647)
A rare hereditary angioedema characterized by potentially life-threatening episodes of subcutaneous and/or submucosal edema without urticaria and with normal levels and function of C1 esterase inhibitor. Patients present with prolonged attacks which last for approximately two to five days and may include nonpitting edema of the skin, severe abdominal symptoms such as pain and swelling, and/or respiratory distress due to upper respiratory airways involvement. Affected locations and frequency of attacks differ slightly between subtypes. Estrogen-containing oral contraceptives and pregnancy are precipitating factors, especially in patients with a factor XII mutation.
Hereditary arginine vasopressin deficiency (ORPHA:30925)
Hereditary central diabetes insipidus is a rare genetic subtype of central diabetes insipidus (CDI, see this term) characterized by polyuria and polydipsia due to a deficiency in vasopressin (AVP) synthesis.
Epidemiology
The prevalence is unknown.
Clinical description
Symptoms usually develop between 1 and 6 years of age but onset in the neonatal period or in elderly patients has been described. They include polyuria, polydipsia and nocturia (often manifesting as enuresis in children). Additional symptoms seen in children can include: lethargy, irritability, growth retardation, weight loss, fever, vomiting or diarrhea. In the autosomal recessive form, symptoms are secondary to reduced biological activity of mutant AVP; heterozygous carriers have subclinical manifestations or are asymptomatic.
Etiology
The origin of the disease is genetic and is usually due to a mutation in the AVP gene located on chromosome 20p13 that encodes a precursor protein consisting of arginine vasopressin and two associated proteins, neurophysin 2 and copeptin. All except a few cases show an autosomal dominant pattern of inheritance. Rarely, an autosomal recessive or X-linked pattern of inheritance is reported.

                            Last update: 
                            July 2012


                            - Expert reviewer(s): 
                            Dr Stefano GHIRARDELLO
Hereditary arterial and articular multiple calcification syndrome (ORPHA:289601)
Hereditary arterial and articular multiple calcification syndrome is a very rare genetic vascular disease of autosomal recessive inheritance, described in less than 20 patients to date, characterized by adult-onset (as early as the second decade of life) isolated calcification of the arteries of the lower extremities (including the iliac, femoral, and tibial arteries) as well as the capsule joints of the fingers, wrists, ankles and feet, and that usually manifests with mild paresthesias of the lower extremities, intense joint pain and swelling, and early onset arthritis of affected joints.
Hereditary benign intraepithelial dyskeratosis (ORPHA:352657)
A rare, genetic, superficial corneal dystrophy disease characterized by white, elevated, epithelial plaques located on the bulbar conjunctiva (sometimes with encroachment of the cornea) and oral mucosa (in any part of the oral cavity), associated with dilated, hyperemic, conjunctival blood vessels, observed mainly in Haliwa-Saponi Native American descendents. Patients may be asymptomatic or present with ocular itching, superficial corneal scarring, excessive lacrimation, photophobia and visual loss due to corneal opacity. Histologically, both ocular and oral lesions display acanthosis with hyperkeratosis and prominent dyskeratosis.
Hereditary breast cancer (ORPHA:227535)
A rare genetic, malignant breast tumor characterized by early onset breast cancer in association with a germline mutation. Tumors arising in carriers of BRCA1 and BRCA2 mutations differ morphologically and genetically from each other, as well as from sporadic breast cancers. Most BRCA1-associated tumors are invasive ductal adenocarcinomas of no special type, typically of higher grade than sporadic tumors, and more often negative for hormone receptors. In addition, more cases with features of typical or atypical medullary carcinoma are seen in these patients. Likewise, BRCA2-associated tumors tend to be of higher grade than sporadic ones, although their phenotype is similar. They show a low frequency of HER-2 expression.
Hereditary bullous dystrophy, macular type (ORPHA:1867)
A rare X-linked syndromic intellectual disability characterized by intellectual deficit, microcephaly, short stature, and ectodermal anomalies (including alopecia, spontaneous formation of bullae without evident trauma, hyper- or hypopigmented maculae, acrocyanosis, and dystrophic nails) in male patients. Additional reported features are short, tapering fingers, ocular anomalies (such as corneal opacities and cataract), and hypogenitalism. There have been no further descriptions in the literature since 1995.
Hereditary butyrylcholinesterase deficiency (ORPHA:132)
Butyrylcholinesterase (BChE) deficiency is a metabolic disorder characterised by prolonged apnoea after the use of certain anaesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anaesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency.
Epidemiology
The prevalence of BChE deficiency is highest in the Caucasian population with between 3.4 and 4% of the population displaying a partial enzyme deficiency leading to slightly prolonged apnoea (between 5 minutes and 1 hour) and 1 in 2500 individuals showing a prolongation of more than 1 hour. Individuals with undetectable levels of BChE activity display a severe prolongation lasting more than 8 hours. The prevalence of this severe form is estimated at 1 in 100 000 individuals.
Etiology
BChE deficiency is a multifactorial disorder. It is caused by mutations in the BChE gene. The BChE gene is located at the E1 locus on chromosome 3 (3q26.1-q26.2) and multiple atypical variants have been identified. However, BChE deficiency and sensitivity to anaesthetic drugs may also occur during pregnancy, in neonates or in association with other pathologies (chronic infections, malnutrition, liver disease, certain cancers etc.).
Diagnostic methods
Diagnosis can be made by analysis of enzyme activity in plasma samples, combined with dibucaine and fluoride inhibition tests. DNA analysis, although not carried out routinely, can be used to identify heterozygous carriers of atypical alleles.
Genetic counseling
The hereditary condition is transmitted as an autosomal recessive trait.
Management and treatment
Affected individuals are asymptomatic unless exposed to neuromuscular blocking agents, however, prolonged respiratory paralysis following anaesthesia makes mechanical ventilation essential until the excess aesthetic agent is metabolised permitting normal neuromuscular function.

                            Last update: 
                            October 2006


                            - Expert reviewer(s): 
                            Pr Pascale DE LONLAY
Hereditary clear cell renal cell carcinoma (ORPHA:422526)
Hereditary clear cell renal cell carcinoma (ccRCC) is a hereditary renal cancer syndrome defined as development of ccRCC in two or more family members without evidence of constitutional chromosome 3 translocation, von Hippel-Lindau disease or other tumor predisposing syndromes associated with ccRCC, such as tuberous sclerosis or Birt-Hogg-Dubbé syndrome.
Hereditary continuous muscle fiber activity (ORPHA:972)
Hereditary continuous muscle fiber activity is a rare, non-dystrophic myopathy characterized by generalized myokymia and increased muscle tone associated with delayed motor milestones, leg stiffness, spastic gait, hyperreflexia and Babinski sign. Symptoms may be worsened by febrile illness or anesthesia.
Hereditary cryohydrocytosis with normal stomatin (ORPHA:398088)
Hereditary cryohydrocytosis with normal stomatin is a rare, hereditary, hemolytic anemia due to a red cell membrane anomaly characterized by fatigue, mild anemia and pseudohyperkalemia due to a potassium leak from the red blood cells. A hallmark of this condition is that red blood cells lyse on storage at 4 degrees centigrade.
Hereditary cryohydrocytosis with reduced stomatin (ORPHA:168577)
A rare hemolytic anemia characterized by combination of neurologic features, such as psychomotor delay, seizures, variable movement disorders, and hemolytic anemia with stomatocytosis, resulting in cation-leaky erythrocytes, pseudohyperkalemia, hemolytic crises and hepatosplenomegaly. Cataracts are also a presenting feature.
Hereditary dentin defect (ORPHA:167759)
The hereditary dentin disorders, dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), comprise a group of conditions characterized by abnormal dentin structure affecting either the primary or both the primary and secondary dentitions.
Epidemiology
DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000 births, whereas that of DD type 1 is 1 in 100,000.
Clinical description
Clinically, the teeth are discolored and show structural defects such as bulbous crowns and small pulp chambers on radiographs. The underlying defect of mineralization often results in shearing of the overlying enamel leaving exposed weakened dentin which is prone to wear. Currently, three subtypes of DGI and two subtypes of DD are recognized but this categorization may change when further causative mutations are identified.
Etiology
DGI type 1 is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD type 1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP).
Diagnostic methods
Diagnosis is based on family history, pedigree construction and detailed clinical examination, but genetic diagnosis may become useful in the future once a sufficient number of disease-causing mutations have been identified.
Differential diagnosis
Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann syndrome, cyclic neutropenia, Chediak-Higashi syndrome, histiocytosis X and Papillon-Lefevre syndrome), permanent teeth discoloration due to tetracyclines, and Vitamin D-dependent and vitamin D-resistant rickets (see these terms).
Genetic counseling
Both DGI and DD are transmitted as autosomal dominant conditions.
Management and treatment
Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a number of options including the use of crowns, over-dentures and dental implants depending on the age of the patient and the condition of the dentition.
Prognosis
Where diagnosis occurs early in life and treatment follows the outlined recommendations, good esthetics and function can be obtained.

                            Last update: 
                            November 2008


                            - Expert reviewer(s): 
                            Dr Martin BARRON  - Pr Mike DIXON  - Dr Iain MACKIE  - Dr Sinead MCDONNELL
Hereditary diffuse gastric cancer (ORPHA:26106)
Hereditary diffuse gastric cancer is a rare epithelial tumor of the stomach, characterized by the development of diffuse (signet ring cell) gastric cancer at a young age, associated with germline heterozygous mutations of CDH1, MAP3K6 and CTNNA1 genes. In early stages it presents with non-specific and vague symptoms, in advanced stages it may cause nausea and vomiting, dysphagia, loss of appetite, abdominal mass or weight loss. Women have an increased risk of lobular breast cancer as well.
Hereditary episodic ataxia (ORPHA:211062)
Hereditary episodic ataxia (EA) represents a group of neurological disorders characterized by recurrent episodes of ataxia and vertigo which may be progressive. Weakness, dystonia and ataxia are sometimes present in the interictal period. Seven types of EA have been described to date (EA type 1 to EA type 7, see these terms), but most of the reported cases belong to EA1 and EA2.
Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome (ORPHA:221043)
Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome is a rare, genetic, hereditary poikiloderma syndrome characterized by early-onset poikiloderma (mainly on the face), hypotrichosis, hypohidrosis, muscle and tendon contractures with varus foot deformity, progressive proximal and distal muscle weakness in all extremities, and progressive pulmonary fibrosis. Mild lymphedema of the extremities, growth retardation, liver impairment, exocrine pancreatic insufficiency and hematologic abnormalities are additional variable features.
Hereditary gastric cancer (ORPHA:423776)
Hereditary gastric cancer refers to the occurrence of gastric cancer in a familial context and is described as two or more cases of gastric cancer in first or second degree relatives with at least one case diagnosed before the age of 50. Familial clustering is observed in 10% of all cases of gastric cancer, and includes hereditary diffuse gastric cancer (early onset diffuse-type gastric cancer), gastric adenocarcinoma and proximal polyposis of the stomach (see these terms) and familial intestinal gastric cancer (familial clustering of intestinal type gastric adenocarcinoma). Hereditary gastric cancer can also occur in other hereditary cancer syndromes such as Lynch syndrome, Li-Fraumeni syndrome, familial adenomatous polyposis and juvenile polyposis syndrome (see these terms).
Hereditary geniospasm (ORPHA:53372)
A rare genetic tremor disorder characterized by recurrent episodes of involuntary tremor of the chin and lower lip due to isolated myoclonus of the mentalis muscle. Patients may present more severe symptoms such as tongue biting and psychological distress. Even though neurological abnormalities are not associated, occasional involvement of sleep disorders and other facial muscles have been described. Sporadic cases were also reported.
Hereditary gingival fibromatosis (ORPHA:2024)
Hereditary gingival fibromatosis (HGF) is a rare benign, slowly progressive, non-inflammatory fibrous hyperplasia of the maxillary and mandibular gingivae that generally occurs with the eruption of the permanent (or more rarely the primary) dentition or even at birth. It presents as a localized or generalized, smooth or nodular overgrowth of the gingival tissues of varying severity. It can be isolated, with autosomal dominant inheritance, or as part of a syndrome.
Hereditary hypercarotenemia and vitamin A deficiency (ORPHA:199285)
Hereditary hypercarotenemia and vitamin A deficiency is an extremely rare metabolic disorder characterized clinically by skin discoloration, elevated levels of carotene and low levels of vitamin A described in fewer than 5 patients to date.