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ALXDRD
MCID: ALX003
MIFTS: 62
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Alexander Disease (ALXDRD)
Categories:
Eye diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
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MalaCards integrated aliases for Alexander Disease:
Characteristics:Orphanet epidemiological data:58
alexander disease
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Japan); Age of onset: All ages; Age of death: any age;
alexander disease type ii
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult,Childhood; Age of death: adult;
alexander disease type i
Inheritance: Not applicable; Age of onset: Infancy,Neonatal; OMIM:56
Inheritance:
autosomal dominant
Miscellaneous:
average age of onset 6 months (range birth - 2 years) death by age 5 (infantile form) three variants distinguished by age of onset - infantile ( onset before age 2), juvenile (onset in childhood), and adult juvenile patients have slower clinical course with preserved intellect, bulbar signs, ataxia, and spasticity adult patients have heterogeneous symptoms including some with relapsing-remitting symptoms similar to multiple sclerosis HPO:31
alexander disease:
Inheritance autosomal dominant inheritance Onset and clinical course infantile onset GeneReviews:24
Penetrance Penetrance appears to be nearly 100% in individuals with the infantile and juvenile forms [li et al 2002, messing & brenner 2003a]....
Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Anatomical: Neuronal diseases Eye diseases Mental diseases
ICD10:
33
Orphanet: 58
Rare neurological diseases
Rare eye diseases External Ids:
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Genetics Home Reference :
25
Alexander disease is a rare disorder of the nervous system. It is one of a group of disorders, called leukodystrophies, that involve the destruction of myelin. Myelin is the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses could be disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.
Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay. Less frequently, onset occurs later in childhood (the juvenile form) or in adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia). Rarely, a neonatal form of Alexander disease occurs within the first month of life and is associated with severe intellectual disability and developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures.
Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the brain and spinal cord (central nervous system).
MalaCards based summary : Alexander Disease, also known as alexander's disease, is related to leukodystrophy and status epilepticus, and has symptoms including seizures and muscle spasticity. An important gene associated with Alexander Disease is GFAP (Glial Fibrillary Acidic Protein), and among its related pathways/superpathways are Proteoglycans in cancer and Regulation of degradation of deltaF508 CFTR in CF. The drugs Metronidazole and Anti-Bacterial Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and eye, and related phenotypes are macrocephaly and agenesis of corpus callosum Disease Ontology : 12 A leukodystrophy that is characterized by the destruction of white matter and the formation of Rosenthal fibers consisting of abnormal clumps of protein that accumulate in astrocytes. NIH Rare Diseases : 52 Alexander disease is a type of leukodystrophy characterized by the destruction of the myelin sheath (the fatty covering that acts as an insulator around nerve fiber) and abnormal protein deposits known as Rosenthal fibers. Most cases of Alexander disease begin before age 2 years (the infantile form). Symptoms of the infantile form include an enlarged brain and head, seizures , stiffness in the arms and/or legs, mental retardation, and delayed physical development. Less frequently, onset occurs later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination. Alexander disease is caused by mutations in the GFAP gene . While this condition is inherited in an autosomal dominant fashion, most cases result from new mutations in the gene. OMIM : 56 In decreasing order of frequency, 3 forms of Alexander disease are recognized, based on age of onset: infantile, juvenile, and adult. Younger patients typically present with seizures, megalencephaly, developmental delay, and spasticity. In older patients, bulbar or pseudobulbar symptoms predominate, frequently accompanied by spasticity. The disease is progressive, with most patients dying within 10 years of onset. Imaging studies of the brain typically show cerebral white matter abnormalities, preferentially affecting the frontal region (Gorospe et al., 2002). All 3 forms have been shown to be caused by mutations in the GFAP gene. (203450) NINDS : 53 Alexander disease is one of a group of neurological conditions known as the leukodystrophies. Leukodystrophies are disorders that result from abnormalities in myelin, the “white matter” that protects nerve fibers in the brain. In Alexander disease, the destruction of white matter is accompanied by the formation of Rosenthal fibers--abnormal clumps of protein that accumulate in non-nerve cells (astrocytes) in the brain. The most common type of Alexander disease is the infantile form that usually begins during the first two years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures. The juvenile form of Alexander disease has an onset between the ages of two and thirteen years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder. The disease occurs in both males and females, and there are no ethnic, racial, geographic, or cultural/economic differences in its distribution. Alexander disease is a progressive and often fatal disease. KEGG : 36 Alexander disease is a rare, but often fatal neurological disorder that has been divided into three subtypes based on the age of onset: the infantile, juvenile and adult forms. The characteristic neuropathological feature of all forms of Alexander's disease is the presence of Rosenthal fibers which include protein aggregates that contain glial fibrillary acidic protein (GFAP) and small stress proteins in astrocytes. UniProtKB/Swiss-Prot : 73 Alexander disease: A rare disorder of the central nervous system. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death within the first decade. Infants with Alexander disease develop a leukodystrophy with macrocephaly, seizures, and psychomotor retardation. Patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. Histologically, Alexander disease is characterized by Rosenthal fibers, homogeneous eosinophilic inclusions in astrocytes. Wikipedia : 74 Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions... more...
GeneReviews:
NBK1172
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Human phenotypes related to Alexander Disease:58 31 (show top 50) (show all 66)
Symptoms via clinical synopsis from OMIM:56Clinical features from OMIM:203450UMLS symptoms related to Alexander Disease:seizures, muscle spasticity MGI Mouse Phenotypes related to Alexander Disease:45
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Drugs for Alexander Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):
Interventional clinical trials:
Cochrane evidence based reviews: alexander disease |
MalaCards organs/tissues related to Alexander Disease:40
Brain,
Spinal Cord,
Eye,
Testes,
Pituitary,
Cortex,
Medulla Oblongata
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Articles related to Alexander Disease:(show top 50) (show all 489)
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Genes related to Alexander Disease (1 elite genes):(show all 23) - Elite gene
- Cancer Census gene in COSMIC
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ClinVar genetic disease variations for Alexander Disease:6 (show top 50) (show all 165)
UniProtKB/Swiss-Prot genetic disease variations for Alexander Disease:73 (show top 50) (show all 62)
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Search
GEO
for disease gene expression data for Alexander Disease.
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Cellular components related to Alexander Disease according to GeneCards Suite gene sharing:
Biological processes related to Alexander Disease according to GeneCards Suite gene sharing:
Molecular functions related to Alexander Disease according to GeneCards Suite gene sharing:
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