TaoMedAI/RareMedData huggingface dataset:
Adult-onset autosomal dominant leukodystrophy (ORPHA:99027)
A rare, slowly progressive neurological disorder involving central nervous system demyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment.
Epidemiology
More than 20 families in different ethnic groups have been reported to date. Exact prevalence and incidence data are however lacking.
Clinical description
Unlike most forms of leukodystrophy which appear in childhood, ADLD occurs in the 4th to 6th decade of life. ADLD may clinically resemble multiple sclerosis in the initial phase. In most patients, the initial manifestation of the disease is autonomic dysfunction resulting in micturition urgency, bladder retention, constipation, postural hypotension and erectile dysfunction in affected males. Decreased sweating is reported in some cases. Some patients develop autonomic dysfunction later in the disease course. The other features are cerebellar dysfunction (gait ataxia, nystagmus, dysmetria, loss of fine motor control, and action tremors), pyramidal signs (spasticity, weakness of both upper and lower extremities, hyperreflexia), and cognitive impairment possibly with personality changes. These manifestations may not develop for years following initial presentation. Neuroradiological characteristics include extensive symmetrical white matter changes, corpus callosum atrophy, and brain stem and spinal cord atrophy. The disease follows a slow progressive course with an eventual loss of walking ability and slightly shortened lifespan.
Etiology
ADLD is caused by chromosomal rearrangements with duplications of the LMNB1 gene (5q23.2) or a ''position effect'' due to a genomic deletion upstream of the gene causing its upregulation. Overexpression of LMNB1 causes myelin disruption in the central nervous system for which the precise underlying pathogenic mechanisms have not been elucidated. Alteration of splicing patterns suggests that ADLD is a spliceopathy.
Genetic counseling
Genetic counseling should be provided to affected families indicating the autosomal dominant pattern of inheritance.

                            Last update: 
                            July 2015


                            - Expert reviewer(s): 
                            Pr Alfredo BRUSCO
Adult-onset autosomal recessive cerebellar ataxia (ORPHA:284289)
A rare, genetic, autosomal recessive cerebellar ataxia disease characterized by adulthood-onset of slowly progressive spinocerebellar ataxia, manifesting with gait and appendicular ataxia, dysarthria, ocular movement anomalies (e.g. horizontal, vertical, and/or downbeat nystagmus, hypermetric saccades), increased deep tendon reflexes and progressive cognitive decline. Additional variable features may include proximal leg muscle wasting and fasciculations, pes cavus, inspiratory stridor, epilepsy, retinal degeneration and cataracts. Brain imaging reveals marked cerebellar atrophy and electromyography shows evidence of lower motor neuron involvement.
Adult-onset autosomal recessive sideroblastic anemia (ORPHA:255132)
A very rare non-syndromic autosomal recessive pyridoxine-refractory sideroblastic anemia due to a splice defect of glutaredoxin-5 (GLRX5) described in a single patient with adult onset microcytic hypochromic anemia with liver iron overload and type 2 diabetes.
Adult-onset cervical dystonia, DYT23 type (ORPHA:420492)
A rare, genetic, isolated dystonia characterized by adult-onset, non-progressive, focal cervical dystonia typically manifesting with torticollis and occasionally accompanied by mild head tremor and essential-type limb tremor.
Adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy (ORPHA:329336)
A rare mitochondrial disease characterized by adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, manifestations of spinocerebellar ataxia (e.g. impaired gait, dysarthria) and mild motor peripheral neuropathy. Respiratory insufficiency has been reported in some cases.
Adult-onset distal myopathy due to VCP mutation (ORPHA:329478)
A rare, genetic distal myopathy disorder characterized by middle age-onset of distal leg muscle weakness, atrophy in the anterior compartment resulting in foot drop, without proximal or scapular skeletal muscle weakness. Rapidly progressive dementia, Paget disease of bone and hand weakness have been reported. Muscle biopsy shows pronounced myopathic changes with rimmed vacuoles.
Adult-onset dystonia-parkinsonism (ORPHA:199351)
A rare neurodegenerative disease usually presenting before the age of 30 and which is characterized by dystonia, L-dopa-responsive parkinsonism, pyramidal signs and rapid cognitive decline.
Epidemiology
Prevalence is unknown. Only 14 cases have been reported to date.
Clinical description
Disease onset occurs in late adolescence or early adulthood (usually before the age of 30) and usually presents with parkinsonism (tremor, rigidity, bradykinesia), dystonia and rapid cognitive decline. Eye movement abnormalities (supranuclear vertical gaze palsy, eyelid opening apraxia), pyramidal tract signs, and psychiatric features such as depression and personality changes have also been reported in some patients. Dopaminergic treatment is initially successful with regard to parkinsonism, but the development of prominent dyskinesias often follows.
Etiology
Adult-onset dystonia-parkinsonism is caused by mutations in the phospholipase A2, group VI (PLA2G6) gene located on chromosome 22q13.1.
Genetic counseling
Adult-onset dystonia-parkinsonism is inherited in an autosomal recessive manner, and genetic counseling is possible and recommended.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Christoph KAMM
Adult-onset immunodeficiency with anti-interferon-gamma autoantibodies (ORPHA:306431)
A rare acquired immunodeficiency disorder characterized by the appearance of susceptibility to disseminated opportunistic infections (in particular, disseminated nontuberculous mycobacterial infection, salmonellosis, penicillosis, and varicella zoster virus infection) in previously healthy (HIV-negative) adults, associated with the presence of acquired autoantibodies to interferon gamma. Typical clinical manifestation includes lymphadenopathy (cervical or generalized), fever, weight loss and/or reactive skin lesions.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ORPHA:313808)
Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia is a rare autosomal dominant disease characterized by a complex phenotype including progressive dementia, apraxia, apathy, impaired balance, parkinsonism, spasticity and epilepsy.
Adult-onset multiple mitochondrial DNA deletion syndrome due to DGUOK deficiency (ORPHA:329314)
An extremely rare multiple mitochondrial DNA deletion syndrome with markedly decreased deoxyguanosine kinase (DGUOK) activity in skeletal muscle characterized by a highly variable phenotype. Clinical manifestations include progressive external ophthalmoplegia, mitochondrial myopathy, recurrent rhabdomyolysis, lower motor neuron disease, mild cognitive impairment, sensory axonal neuropathy, optic atrophy, ataxia, hypogonadism and/or parkinsonism.
Adult-onset nemaline myopathy (ORPHA:171442)
A rapidly progressive type of nemaline myopathy (NM) characterized by a very late onset.
Epidemiology
The annual incidence of NM has been estimated at 1/50,000 live births. Adult-onset NM represents <5% of total cases.
Clinical description
Adult onset NM occurs sporadically between 20 and 50 years of age. It presents with a generalized weakness, myalgia and rapid progression. Several cases have been associated with cardiomyopathy, dropped head syndrome and respiratory involvement. Muscle biopsy can reveal inflammatory changes. Monoclonal gammopathy and paresthesiae may be a marker of poor prognosis.
Etiology
This form of NM is due to mutations in the ACTA1 (1q42.13), NEB (2q22), TPM2 (9p13.3) or TPM3 (1q21.2) genes.
Genetic counseling
Adult onset NM is usually sporadic and no familial history of neuromuscular diseases is found.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Dr Monique RYAN
AFib amyloidosis (ORPHA:93562)
A rare, hereditary amyloidosis with primary renal involvement characterized by fibrinogen A-alpha-chain amyloid deposition predominantly in the kidney glomeruli and clinically presenting with hypertension, uremia, nephrotic syndrome slowly progressing to end-stage renal disease. Extra-renal involvement is possible, due to neurological, cardiac, visceral and vascular amyloid deposition.
African tick typhus (ORPHA:101334)
A rare bacterial infectious disease caused by the tick-borne bacterium Rickettsia africae, characterized by acute onset of fever accompanied by myalgia, localized lymphadenitis, and a papulovesicular rash. In most cases at least one, sometimes multiple, inoculation eschars are observed. Clustering of cases is frequent.
African trypanosomiasis (ORPHA:3385)
A rare parasitic disease characterized by infection with the protozoans Trypanosoma brucei rhodesiense (East African trypanosomiasis) or T. brucei gambiense (West African trypanosomiasis), usually due to the bite of an infected tsetse fly. The first, hemolymphatic stage presents with fever, headaches, fatigue, lymphadenopathy, and aching muscles and joints. In East African trypanosomiasis, the fly bite may develop into a red sore or chancre. This form then progresses to CNS invasion with somnolence and other neurologic and psychiatric symptoms within a few weeks, while West African trypanosomiasis slowly progresses within about 3 years. Both forms are fatal if left untreated.
Agammaglobulinemia-microcephaly-craniosynostosis-severe dermatitis syndrome (ORPHA:83617)
A rare syndromic agammaglobulinemia characterized by profound B-cell depletion (with normal T-cell numbers) resulting in agammaglobulinemia, associated with severe developmental delay, microcephaly, craniosynostosis, cleft palate, narrowing of the choanae, blepharophimosis, and severe dermatitis. Additional reported features include distal joint contractures, renal/genitourinary anomalies, and mild cerebral atrophy, among others.
AGel amyloidosis (ORPHA:85448)
A rare, systemic amyloidosis characterized by a triad of ophthalmologic, neurologic and dermatologic findings due to the deposition of gelsolin amyloid fibrils in these tissues. Clinical manifestations include corneal lattice dystrophy, cranial neuropathy, especially affecting the facial nerve, bulbar signs, cutis laxa, increased skin fragility, and less commonly peripheral neuropathy and renal failure.
Agenesis of the superior vena cava (ORPHA:99114)
A rare congenital anomaly of the great veins characterized by unilateral or bilateral complete absence of the superior vena cava (SVC). Unilateral agenesis is mainly asymptomatic (most of the time diagnosed incidentally) and patients usually have otherwise normal heart structure. Bilateral agenesis, however, is frequently associated with other congenital cardiac anomalies and/or conduction abnormalities (such as tetralogy of Fallot, atrial septal defect) and typically present symptoms of SVC syndrome.
Aggressive NK-cell leukemia (ORPHA:86873)
An extremely rare and highly aggressive neoplasm, usually manifesting in the third to fourth decade of life, affecting males and females equally, and characterized by the onset of high fever, weight loss, jaundice, skin infiltration, lymphadenopathy, hepatosplenomegaly, and severe anemia. It has a fulminant and rapidly fatal disease course with the progressive appearance of multiorgan failure and disseminated intravascular coagulation.
Agnathia-holoprosencephaly-situs inversus syndrome (ORPHA:990)
An extremely rare and fatal association syndrome, characterized by absence of the mandible, cerebral malformations with facial anomalies related to a defect in cleavage in the embryonic brain (e.g. synophthalmia, malformed and low-set ears fused in midline (otocephaly), agenesis of the olfactory bulbs, microstomia, hypoglossia/aglossia) and situs inversus partialis or totalis.
AH amyloidosis (ORPHA:442582)
A rare, systemic amyloidosis characterized by the aggregation and deposition of amyloid fibrils composed of monoclonal immunoglobulin heavy-chain fragments, usually produced by a plasma cell neoplasm. Amyloid fibrils deposit in various organs, most commonly in the kidneys. It typically affects older patients and clinical presentation includes signs and symptoms of renal dysfunction, sometimes leading to nephrotic syndrome and end stage renal disease. Cardiac, liver and nerves involvement has also been described.
AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome (ORPHA:412069)
A rare, syndromic intellectual disability characterized by hypotonia, developmetal delay, absent or severly delayed speech development, intellectual disability, obstructive sleep apnea, mild dysmorphic facial features and behavioral abnormalities. Epilepsy, ataxia and nystagmus have also been reported.
AIDS wasting syndrome (ORPHA:90081)
A rare condition associated with acquired immunodeficiency syndrome (AIDS) and characterized by unwanted weight loss (involving both fat and muscle) of more than ten percent of body weight, with either diarrhea or weakness and fever which have lasted at least 30 days and are not related to an infection.
Airway infantile hemangioma (ORPHA:137935)
A rare benign vascular tumor characterized by rapid growth after birth (followed by spontaneous partial regression over the course of years), potentially leading to life-threatening airway obstruction due to the subglottic location. Patients present with respiratory symptoms including biphasic stridor, recurrent croup, cyanosis, apnea, and sternal and intercostal retractions. The tumor may be accompanied by cutaneous hemangiomata, especially in the lower facial ("beard") distribution.
AKT2-related familial partial lipodystrophy (ORPHA:79085)
A rare familial partial lipodystrophy characterized by adult onset of distal lipoatrophy and severe insulin resistance in the liver and peripheral tissues, hyperinsulinemia, and diabetes mellitus. Acanthosis nigricans and hypertension have been reported in association.
Alacrimia-choreoathetosis-liver dysfunction syndrome (ORPHA:404454)
A rare, genetic, inborn error of metabolism disorder characterized by global developmental delay, hypotonia, choreoathetosis, hypo-/alacrimia, and liver dysfunction which manifests with elevated liver transaminases and hepatocyte cytoplasmic storage material or vacuolization on liver biopsy. Additional features reported include acquired microcephaly, hypo-/areflexia, seizures, peripheral neuropathy, intellectual and language/speech disability, additional ocular anomalies and EEG and brain imaging abnomalities.
Alar cartilages hypoplasia-coloboma-telecanthus syndrome (ORPHA:2007)
A very rare dysmorphic disorder characterized by hypoplasia and coloboma of the alar cartilages and telecanthus described in 2 sisters. No new cases with similar features have been reported since 1976.
Albers-Schönberg osteopetrosis (ORPHA:53)
A sclerosing disorder of the skeleton characterized by increased bone density that classically displays the radiographic sign of ''sandwich vertebrae'' (dense bands of sclerosis parallel to the vertebral endplates).
Epidemiology
The prevalence is estimated to be 1/20,000.
Clinical description
Onset of the disease is typically in late childhood or adolescence. The main manifestations are confined to the skeleton, including fractures, scoliosis, hip osteoarthritis and osteomyelitis, particularly affecting the mandible in association with dental abscess or caries. Cranial nerve compression is a rare but important complication, with hearing and visual loss affecting around 5% of individuals. Moderate bone marrow failure is described occasionally.
Etiology
The disease is caused by heterozygous mutations in the chloride channel 7 (ClCN7) gene (16p13).
Diagnostic methods
Diagnosis is based on clinical findings and largely depends on the radiographic appearance of the skeleton. Genetic testing is available and can be used to confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes other subtypes of osteopetrosis, fluorosis, beryllium, lead and bismuth poisoning, myelofibrosis, Paget's disease (sclerosing form) and malignancies (lymphoma, osteoblastic cancer metastases) (see these terms).
Antenatal diagnosis
Antenatal diagnosis is possible if the mutation causing the condition in the family is known.
Genetic counseling
Albers-Schönberg osteopetrosis is transmitted in an autosomal dominant manner. Genetic counseling should be offered to families. Each child of an affected individual has 50% risk of being affected. The parents of the proband should be carefully evaluated for signs of osteopetrosis, including radiographic studies of the skeleton.
Management and treatment
At present, there is no effective medical treatment for osteopetrosis. Management is supportive and aims at providing multidisciplinary surveillance and symptomatic treatment.
Prognosis
Clinical manifestations may worsen over time but life expectancy is usually normal.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Dr Ravi SAVARIRAYAN  - Dr Zornitza STARK
Albinism-deafness syndrome (ORPHA:998)
A rare disorder characterised by congenital nerve deafness and piebaldness with no ocular albinism. It has been described in one large pedigree. Transmission is X-linked with affected males presenting with profound sensorineural deafness and severe pigmentary abnormalities of the skin, and carrier females presenting with variable hearing impairment without any pigmentary changes. The causative gene has been mapped to Xq26.3-q27.1.
ALDH18A1-related De Barsy syndrome (ORPHA:35664)
A rare, genetic, neurometabolic disease characterized by prenatal and postnatal growth retardation, hypotonia, failure to thrive, large and late-closing fontanel, development delay, cutis laxa, joint laxity, progeroid appearance, and dysmorphic facial features. In addition, corneal opacities, cataracts, myopia, seizures, hyperreflexia and athetoid movements have also been associated.
ALECT2 amyloidosis (ORPHA:439224)
A rare, systemic amyloidosis characterized by slowly progressive renal disease presenting with proteinuria, hypertension and decreased glomerular filtration rate leading to progressive renal failure. Histology reveals amyloid deposits of leukocyte chemotactic factor-2 protein in the renal cortical interstitium, tubular basement membranes, glomeruli and the vessel walls. Extra-renal deposits can be seen in the liver, lungs, spleen and adrenal glands.
Alexander disease (ORPHA:58)
A rare neurodegenerative disorder of the astrocytes comprised of two clinical forms: Alexander disease (AxD) type I and type II manifesting with various degrees of macrocephaly, spasticity, ataxia and seizures and leading to psychomotor regression and death.
Epidemiology
The prevalence is unknown. One population based study in Japan estimated an annual incidence of 1/ 2.7 million.
Clinical description
The clinical presentation depends on the subtype. Previously, AxD was classified either as infantile, juvenile or adult, based simply on age of onset. The currently used classification system is based on a constellation of clinical and radiologic features and includes AxD type I and AxD type II (see these terms). AxD type I is more likely to be of early onset (mean 1.74 years) and shorter survival (median 14 years) whereas type II exhibits onset throughout the lifespan (mean 21.64 years, but can occur in early childhood) and has longer survival (median 25 years). The two types also differ in their clinical symptoms. AxD type I manifests with symptoms of encephalopathy, epilepsy and failure to thrive and has an infantile presentation, while patients with AxD type II manifest with bulbar, autonomic and motor signs such as dysarthria, dysphonia, dysphagia, ataxia, spastic paraparesis and palatal myoclonus. AxD type II also has a slower progression and cognitive impairment can be completely absent.
Etiology
In the vast majority (95%) of patients, AxD is caused by gain-of-function de novo mutations in the glial fibrillary acidic protein (GFAP) gene. Several familial cases have also been reported with autosomal dominant transmission. This gene encodes GFAP, the major intermediate filament protein found in astrocytes. The over-expression and accumulation of this mutant protein leads to the formation of astrocytic inclusion bodies (Rosenthal fibers) throughout the central nervous system (CNS). It is currently unknown how Rosenthal fibers are involved in disease pathogenesis.

                            Last update: 
                            June 2013


                            - Expert reviewer(s): 
                            Dr Albee MESSING  - Dr Adeline VANDERVER
ALG1-CDG (ORPHA:79327)
A severe form of congenital disorders of N-linked glycosylation characterized by severe developmental and psychomotor delay, muscular hypotonia, intractable early-onset seizures, and microcephaly. Additional features include altered blood coagulation with a high probability of hemorrhages or thromboses, nephrotic syndrome, ascites, hepatomegaly, cardiomyopathy, ocular manifestations (strabismus, nystagmus), and immunodeficiency. The disease is caused by loss-of-function mutations in the gene ALG1 (16p13.3).
ALG11-CDG (ORPHA:280071)
A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (microcephaly, high forehead, low posterior hairline, strabismus), hypotonia, failure to thrive, intractable seizures, developmental delay, persistent vomiting and gastric bleeding. Additional features that may be observed include fat pads anomalies, inverted nipples, and body temperature oscillation. The disease is caused by mutations in the gene ALG11 (13q14.3).
ALG12-CDG (ORPHA:79324)
A form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. The disease is caused by loss of function mutations of the gene ALG12 (22q13.33).
ALG13-CDG (ORPHA:324422)
A form of congenital disorders of N-linked glycosylation characterized by microcephaly, hepatomegaly, edema of the extremities, intractable seizures, recurrent infections and increased bleeding tendency. The disease is caused by mutations in the gene ALG13 (Xq23).
ALG2-CDG (ORPHA:79326)
A form of congenital disorders of N-linked glycosylation characterized by iris coloboma, cataract, infantile spasms, developmental delay and abnormal coagulation factors. The disease is caused by loss-of-function mutations in the gene ALG2 (9q31.1). Transmission is autosomal recessive.
ALG3-CDG (ORPHA:79321)
A form of congenital disorders of N-linked glycosylation characterized by severe neurological involvement, including hypotonia, developmental delay, intellectual disability, postnatal microcephaly, and progressive brain and cerebellar atrophy. Epilepsy with hypsarrythmia is frequently reported. Additional features that may be observed include failure to thrive, arthrogryposis multiplex congenita (AMC), vision impairment (optic atrophy, iris coloboma) and facial dysmorphism (hypertelorism with a broad nasal bridge, large and thick ears, thin lips, micrognathia). The disease is caused by loss of function mutations of the gene ALG3 (3q27.3).