TaoMedAI/RareMedData huggingface dataset:
ALG6-CDG (ORPHA:79320)
A form of congenital disorders of N-linked glycosylation characterized by feeding problems, mild-to-moderate neurologic involvement with hypotonia, poor head control, developmental delay, ataxia, strabismus, and seizures, ranging from febrile convulsions to epilepsy. Retinal degeneration has also been reported. A minority of patients show other manifestations, particularly intestinal (such as protein-losing enteropathy) and liver involvement. The disease is caused by loss of function mutations of the gene ALG6 (1p31.3).
ALG8-CDG (ORPHA:79325)
A rare form of congenital disorders of N-linked glycosylation characterized by gastrointestinal symptoms (diarrhea, vomiting, feeding problems with failure to thrive, protein-losing enteropathy), edema and ascites (including hydrops fetalis), hepatomegaly, renal tubulopathy, coagulation anomalies due to thrombocytopenia, brain involvement (psychomotor delay, seizures, ataxia), facial dysmorphism (low-set ears and retrognathia), pes equinovarus, and muscular hypotonia. Cataracts may also be observed. Prognosis is usually poor. The disease is caused by loss-of-function mutations in the gene ALG8 (11q14.1), resulting in a block in the initial step of protein glycosylation.
ALG9-CDG (ORPHA:79328)
A rare form of congenital disorders of N-linked glycosylation characterized by progressive microcephaly, hypotonia, developmental delay, drug-resistant infantile epilepsy, and hepatomegaly. Additional features that may be observed include failure to thrive, pericardial effusion, renal cysts, skeletal dysplasia, facial dysmorphism (frontal bossing, hypertelorism, depressed nasal bridge, low-seated ears, large mouth) and hydrops fetalis. The disease is caused by loss-of-function mutations in the gene ALG9 (11q23).
ALK-negative anaplastic large cell lymphoma (ORPHA:300903)
A type of ALCL, a rare and aggressive peripheral T-cell non-Hodgkin lymphoma affecting lymph nodes and extranodal sites, which is characterized by the lack of expression of a protein called anaplastic lymphoma kinase (ALK).
Epidemiology
The prevalence of ALK- ALCL is unknown. This subtype is more commonly found in patients over the age of 40.
Clinical description
ALK- ALCL is characterized by peripheral, mediastinal, or abdominal lymph node involvement. It manifests with the development of painless,enlarged lymph nodes, especially in the neck or armpit (axillary lymph nodes). General symptoms include loss of appetite and fatigue as well as fever, weight loss, and night sweats (B symptoms). Mediastinal involvement manifests as cough, dypsnea and/or edema. ALK- ALCL can also extend to extranodal sites such as the bones, bone marrow, subcutaneous tissue, lungs, spleen and liver. The 5-year survival for ALK-negative patients is of 33-49%.
Etiology
Etiology is unknown.

                            Last update: 
                            March 2014


                            - Expert reviewer(s): 
                            Dr Pauline BRICE
ALK-positive anaplastic large cell lymphoma (ORPHA:300895)
A type of ALCL, a rare and aggressive peripheral T-cell non-Hodgkin lymphoma affecting lymph nodes and extranodal sites, which is characterized by the expression of a protein called anaplastic lymphoma kinase (ALK).
Epidemiology
The prevalence of ALK+ ALCL is unknown. This subtype usually affects children and young adults.
Clinical description
ALK+ ALCL is characterized by peripheral, mediastinal, or abdominal lymph node involvement. It manifests with the development of painless, enlarged lymph nodes, especially in the neck or armpit (axillary lymph nodes). General symptoms include loss of appetite and fatigue as well as fever, weight loss, and night sweats (B symptoms). Mediastinal involvement manifests as cough, dypsnea and/or edema. ALK+ ALCL can also extend to extranodal sites such as the bones, bone marrow, subcutaneous tissue, lungs, spleen and liver. The 5-year survival rate of ALK-positive patients is 70-80%.
Etiology
In ALK+ ALCL, the anaplastic lymphoma receptor tyrosine kinase ALK>/i> gene is overexpressed due to a t(2;5) (p23;q35) translocation.

                            Last update: 
                            March 2014


                            - Expert reviewer(s): 
                            Dr Pauline BRICE
ALK-positive large B-cell lymphoma (ORPHA:364043)
A very rare variant of diffuse large B-cell lymphoma (DLBCL) mainly affecting middle-aged immunocompetent men and characterized by a consistent primary involvement of lymph nodes (mainly in the cervical and mediastinum lymph nodes) and with infrequent extra nodal involvement of the bone marrow and other extra-nodal sites (head and neck region, liver, spleen, and gastrointestinal tract). It has an aggressive disease course, and is associated with a poor prognosis.
Alkaline ceramidase 3 deficiency (ORPHA:502444)
A rare genetic leukodystrophy characterized by infantile onset of stagnation and regression of motor and language development resulting in complete lack of communication and purposeful movement. Further neurological manifestations include truncal hypotonia, appendicular spasticity, dystonia, optic disc pallor, peripheral neuropathy, and neurogenic bladder. Patients also present multiple contractures, late-onset relative macrocephaly, short stature, and facial dysmorphism (including coarse facial features, sloping forehead, thick eyebrows, low-set ears, prominent nose, flat philtrum, and prominent lower lip). Brain imaging at advanced stages shows diffuse abnormal white matter signal and severe atrophy. Sural nerve biopsy reveals decreased myelination.
Alobar holoprosencephaly (ORPHA:93925)
A severe form of holoprosencephaly characterized by a single brain ventricle and no interhemispheric fissure. Severe craniofacial features may manifest as cyclopia, ethmocephaly or cebocephaly.
Alopecia antibody deficiency (ORPHA:1006)
A rare primary immunodeficiency disorder characterized by the association of alopecia areata totalis and antibody deficiency (congenital agammaglobulinemia or incomplete antibody deficiency syndrome), manifesting with recurrent infections. There have been no further descriptions in the literature since 1976.
Alopecia totalis (ORPHA:700)
A form of alopecia areata, an inflammatory disease of the hair follicle, characterized by a complete loss of hair of the entire scalp which becomes glabrous.
Alopecia universalis (ORPHA:701)
A disorder of most severe form of alopecia areata, an inflammatory disease of the hair follicle, which is characterized by a complete loss of hair of the scalp and all the hair-bearing areas of the body.
Alopecia-contractures-dwarfism-intellectual disability syndrome (ORPHA:1005)
A form of ectodermal dysplasia syndrome characterized by a short stature of prenatal onset, alopecia, ichthyosis, photophobia, ectrodactyly, seizures, scoliosis, multiple contractures, fusions of various bones (particularly elbows, carpals, metacarpals, and spine), intellectual disability, and facial dysmorphism (microdolichocephaly, madarosis, large ears and long nose). ACD syndrome overlaps with ichthyosis follicularis-alopecia-photophobia syndrome.
Alopecia-epilepsy-pyorrhea-intellectual disability syndrome (ORPHA:1008)
A rare genetic syndromic intellectual disability that is characterized by congenital permanent alopecia universalis, intellectual disability, psychomotor epilepsy and periodontitis (pyorrhea). Total permanent alopecia and pyorrhea are invariably concomitant while intellectual disability and psychomotor epilepsy are observed in most patients. No other abnormality of nails or skin (apart from absence of hair) has been reported. Transmission is autosomal dominant.
Alopecia-intellectual disability syndrome (ORPHA:2850)
An extremely rare genetic syndromic intellectual disability described in less than 20 families to date and characterized by total or partial alopecia associated with intellectual deficit. The syndrome can be associated with other anomalies such as seizures, sensorineural hearing loss, delayed psychomotor development, and/or hypertonia.
Alopecia-intellectual disability-hypergonadotropic hypogonadism syndrome (ORPHA:1014)
A rare multiple congential anomalies syndrome characterized by association of congenital total alopecia, mild intellectual deficit and hypergonadotropic hypogonadism.
Alpha delta granule deficiency (ORPHA:734)
A rare hemorrhagic disorder due to a constitutional platelet anomaly characterized by moderate to severe deficiency in both platelet alpha-granules and dense bodies, resulting in impaired platelet function and decreased aggregation responses. Patients present increased bleeding tendency with symptoms like easy bruising, or menorrhagia.
Alpha-B crystallin-related late-onset myopathy (ORPHA:399058)
A rare, genetic, alpha-crystallinopathy disease characterized by adult-onset myofibrillar myopathy, variably associated with cardiomyopathy and/or posterior polar cataracts. Patients typically present progressive proximal and distal muscle weakness and wasting of lower and upper limbs, often with velopharyngeal involvement including dysphagia, dysphonia and ventilatory insufficiency. Electromyography shows myopathic features and muscle biopsy reveals myofibrillar myopathy changes.
Alpha-dystroglycan-related limb-girdle muscular dystrophy R16 (ORPHA:280333)
A form of limb-girdle muscular dystrophy characterized by slowly-progressive, mainly proximal, muscle weakness presenting in early childhood (with difficulties walking and climbing stairs) and mild to severe intellectual disability. Additional manifestations reported include microcephaly, mild increase in thigh or calf muscles, and contractures of the ankles.
Alpha-heavy chain disease (ORPHA:100025)
A type of HCD characterized by the production of incomplete monoclonal alpha-heavy chains without associated light chains. Alpha-HCD is considered to be a subtype of immunoproliferative small intestinal disease (IPSID). The clinical presentation includes chronic diarrhea with evidence of malabsorption.
Epidemiology
The prevalence of the disease is unknown but most cases have been from North African and Middle Eastern/Mediterranean countries and have been associated with poor sanitation. There have been more than 400 cases reported in the world literature.
Clinical description
Alpha-HCD has a predilection for young age groups (20-30 years). Patients present with symptoms of malabsorption. Diarrhea, weight loss and abdominal pain are common. Parasitic infections are often present. Infiltration of the jejunal mucosa with plasmacytoid cells is the most frequent pathologic feature. Immunoblastic lymphoma occurs as the disease progresses.
Etiology
The exact cause of alpha-HCD is unknown. The lymphoplasmacytic infiltration of the intestinal mucosa is felt to be a response of the alimentary tract immune system to prolonged luminal antigenic stimulation by intestinal organisms.
Diagnostic methods
The diagnosis of alpha-HCD is based on identification of free alpha-heavy chains without associated light chains. Truncated alpha-heavy chains can be detected in biological fluids (serum, urine, jejunal secretions) by immunoelectrophoresis, immunoselection, or immunofixation.
Differential diagnosis
Alpha-HCD disease must be differentiated from non-Hodgkin lymphoma (NHL; see this term), although this is an uncommon diagnosis in the age range typical of alpha-HCD. Other causes of small bowel malabsorption need to be considered, especially celiac disease (see this term).
Management and treatment
Initial treatment consists of eradication of any concurrent infection (e.g., parasites, viruses, Helicobacter pylori, Campylobacter jejuni) with appropriate antibiotics. For patients with symptomatic disease not responding adequately to antibiotics, chemotherapy similar to that used to treat NHL is recommended. Surgical resection is sometimes needed when bulky masses are present.
Prognosis
The disease course of alpha-HCD is variable and long-term prognosis of the disease is imprecise. Without antibiotics and chemotherapy the disease progresses rapidly and prognosis is poor.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Pr Robert KYLE  - Dr Dietlind WAHNER-ROEDLER
Alpha-mannosidosis (ORPHA:61)
An inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual deficit.
Epidemiology
It occurs in approximately 1 in 500,000 live births.
Clinical description
Affected infants often appear normal at birth but their condition worsens progressively. However, some children are born with ankle equinus or develop hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent infections, especially in the first decade of life), skeletal abnormalities (mild-to-moderate dysostosis multiplex, scoliosis and deformation of the sternum), hearing impairment (moderate-to-severe sensorineural hearing loss), gradual impairment of mental functions and speech, and often, periods of psychosis. Associated motor function disturbances include muscular weakness, joint abnormalities and ataxia. The facial dysmorphism is marked by a large head with a prominent forehead, rounded eyebrows, a flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight strabismus is common. The clinical variability is significant, representing a continuum in severity.
Etiology
The disorder is caused by lysosomal alpha-mannosidase deficiency. It is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12).
Diagnostic methods
Diagnosis is made by measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic.
Differential diagnosis
The principle differential diagnoses are other lysosomal storage diseases, such as the various forms of mucopolysaccharidosis (see these terms).
Antenatal diagnosis
Antenatal diagnosis is possible, based on both biochemical and genetic methods.
Genetic counseling
Alpha-mannosidosis is inherited in an autosomal recessive fashion. Genetic counseling should be provided to explain the nature of the disease and to detect carriers.
Management and treatment
Management should be proactive, preventing complications and treating manifestations. Infections must be treated frequently. Otolaryngological treatment of fluid in the middle ear is often needed and use of hearing aids is invariably required. Early educational intervention for development of social skills is needed and physiotherapy is important to improve bodily function. Orthopedic surgery may be necessary.
Prognosis
The long-term prognosis is poor. There is an insidiously slow progression of neuromuscular and skeletal deterioration over several decades, making most patients wheel-chair dependent. No patients manage to be completely socially independent. However, many patients survive to over 50 years of age.

                            Last update: 
                            July 2016


                            - Expert reviewer(s): 
                            Pr Dag MALM  - Pr Oivind NILSSEN
Alpha-N-acetylgalactosaminidase deficiency type 1 (ORPHA:79279)
A very rare and severe type of NAGA deficiency characterized by infantile neuroaxonal dystrophy.
Epidemiology
Prevalence of this disorder is not known but less than 20 cases have been reported to date for NAGA deficiency
Clinical description
The disease presents with psychomotor retardation at around 9 months of age and later, at the age of 2, with developmental retrogression. Further manifestations follow between the ages of 4-10 years, including muscular hypotonia, spasticity, nystagmus, strabismus, myoclonic jerks, grand-mal seizures, cortical blindness and deafness, optic and brain atrophy, loss of environmental contact and decorticate posturing. No visceromegaly or coarsening of features has been reported.
Etiology
NAGA deficiency type 1 is caused by a homozygous NAGA gene (22q13.2) mutation resulting in a Glu325-to-Lys (E325K) substitution and the dysfunction, instability and rapid degradation of the lysosomal protein NAGA.
Genetic counseling
Transmission is autosomal recessive and genetic counseling is possible.

                            Last update: 
                            June 2013
Alpha-N-acetylgalactosaminidase deficiency type 2 (ORPHA:79280)
A very rare mild adult type of NAGA deficiency with the features of angiokeratoma corporis diffusum and mild sensory neuropathy.
Epidemiology
Prevalence of this disorder is not known but less than 20 cases have been reported to date for NAGA deficiency.
Clinical description
This disorder is clinically heterogeneous. Some patients have been reported to have, in addition to angiokeratoma, mild intellectual impairment, but no neurologic signs. Another patient had lymphedema, cardiomegaly, corneal opacity and slight facial coarsening including thick lips, a depressed nasal bridge and an enlarged tip of the nose. Other facultative features consist of tinnitus, hearing loss and vertigo (Meniere disease) (see this term). Pathological characteristics are comprised of vacuolization seen in the blood and dermal cells including the endothelial cells of blood and lymphatic vessels, pericytes, fibrocytes, fat cells, Schwann cells, axons, arrector pili smooth muscle cells, and eccrine sweat gland cells. Vacuolization is most prominent in vascular endothelial cells and the secretory portion of sweat glands.
Etiology
Different causal homozygous mutations of the NAGA gene (22q13.2) have been described in the reported patients. These mutations lead to the dysfunction, instability and rapid degradation of the lysosomal protein, NAGA. Lack of this enzyme activity leads to impaired catabolism and accumulation of undegraded glycoconjugates in the tertiary lysosomes.
Genetic counseling
Transmission is autosomal recessive and genetic counseling is possible.

                            Last update: 
                            June 2013
Alpha-N-acetylgalactosaminidase deficiency type 3 (ORPHA:79281)
A rare clinically heterogeneous type of NAGA deficiency with developmental, neurologic and psychiatric manifestations presenting at an intermediate age.
Epidemiology
Prevalence of this disorder is not known but less than 20 cases have been reported to date for NAGA deficiency
Clinical description
A very wide spectrum of signs, with a juvenile onset, has been described including asymptomatic patients at the time of diagnosis. Manifestations seen in clinically overt cases may include epilepsy of variable severity, psychomotor retardation, intellectual impairment, autism, strabismus and cataract.
Etiology
Compound heterozygous or homozygous mutations of the alpha-N-acetylgalactosaminidase gene (NAGA; 22q13.2) have been reported in affected patients but also occasionally in their healthy siblings. These mutations lead to the dysfunction, instability and rapid degradation of the lysosomal protein NAGA.
Genetic counseling
Transmission is autosomal recessive and genetic counseling is possible.

                            Last update: 
                            June 2013
Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 (ORPHA:62)
A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by childhood onset of progressive proximal weakness of the shoulder and pelvic girdle muscles, resulting in difficulty walking, scapular winging, calf hypertrophy and contractures of the Achilles tendon, which lead to a tiptoe gait pattern. Cardiac and respiratory involvement is rare.
Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16 (ORPHA:98791)
A rare developmental defect during embryogenesis, a contiguous gene deletion syndrome, is a form of alpha-thalassemia characterized by microcytosis, hypochromia, normal hemoglobin (Hb) level or mild anemia, associated with developmental abnormalities.
Epidemiology
Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16 (ATR-16) prevalence is unknown. More than 20 cases have been reported to date.
Clinical description
ATR-16 is a congenital disease. Patients present with either alpha-thalassemia trait or mild hemoglobin H disease (HbH disease) associated with a mild to profound (in most cases) intellectual disability and, in some cases, with mild, nonspecific dysmorphic features (mild hypertelorism, down slanted palpebral fissures, broad or prominent nasal bridge, small ears, short neck), microcephaly and short stature. Genital abnormalities (hypospadias and cryptorchidism) have been reported in males. Club foot is common.
Etiology
ATR-16 is due to large deletions on chromosome band 16p13.3 which remove the alpha-globin genes (HBA1 and HBA2), and many other flanking genes. The gene(s) responsible for intellectual deficiency and other developmental abnormalities has not been clearly identified. All cases are due to de novo deletions or segregation for parental translocations inherited in an unbalanced manner.
Diagnostic methods
Diagnosis is based on the clinical picture and confirmed by cytogenetic testing. Routine cytogenetic studies may be sufficient to identify the deletion. However, in some instances other methods such as comparative genomic hybridization (CGH) arrays are used to detect cryptic subtelomeric deletions.
Differential diagnosis
Differential diagnosis includes Alpha thalassemia - X-linked intellectual deficit syndrome, and the co-occurrence of common alpha-thalassemia trait and an intellectual deficiency of another cause.
Antenatal diagnosis
Antenatal diagnosis is indicated in cases of parental translocations but it can also be offered to parents of a patient with de novo deletions to prevent recurrence due to germline mosaicism.
Genetic counseling
Genetic counseling is possible when parents are known carriers of the chromosomal translocation.
Management and treatment
There is no treatment for ATR-16. Management is symptom-based and requires a multidisciplinary approach. Management of intellectual deficiency usually includes speech therapy and individualized educational plans. In case of anemia, specific treatment may include occasional red blood cell transfusions, iron chelation and other supportive measures.
Prognosis
The prognosis is highly variable, depending on the degree of intellectual deficiency.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Pr Catherine BADENS