Alexander Disease

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OMIM 57 203450 Disease Ontology 12 DOID:4252 MeSH 44 D038261 NCIt 50 C84545 SNOMED-CT 68 81854007 Orphanet 59 ORPHA58 ORPHA363722 ORPHA363717 MESH via Orphanet 45 D038261

UMLS via Orphanet 74 C0270726 ICD10 via Orphanet 34 E75.2 MedGen 42 C0270726 KEGG 37 H00065 SNOMED-CT via HPO 69 263681008 27272007 230745008 95427009 11934000 563001 24982008 18963009 21061000119107 35489007 78667006 73211009 40930008 24184005 38341003 123527003 400179000 312894000 78441005 161857006 312230002 364538006 415690000 415691001 52613005 228156007 247578003 91138005 128613002 246545002 313307000 84757009 91175000 85102008 398151007 398152000 221360009 397790002 8011004 5102002 22325002 26079004 19410003 36440009 432788009 47004009 95281009 90145001 288939007 40739000 16932000 14760008 225595004 386689009 271700006 409623005 36649002 274521009 20301004 609225004 45170000 11538006 15241006 17944005 72042002 45007003 111266001 64217002 414564002 249710008 61960001 14648003 73430006 193093009 95666008 65958008 248062006 more UMLS 73 C0270726 C2930798

NINDS : ⁵⁴ 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. 

MalaCards based summary : Alexander Disease, also known as alexander's disease, is related to leukodystrophy and leukoencephalopathy, hereditary diffuse, with spheroids, and has symptoms including muscle spasticity and seizures. An important gene associated with Alexander Disease is GFAP (Glial Fibrillary Acidic Protein), and among its related pathways/superpathways are Cytoskeleton remodeling Neurofilaments and ATM Signaling Network in Development and Disease. Affiliated tissues include brain, eye and cortex, and related phenotypes are macrocephaly and short neck

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.

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.

NIH Rare Diseases : ⁵³ 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 : ⁵⁷ 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)

UniProtKB/Swiss-Prot : ⁷⁵ 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 : ⁷⁶ Alexander disease is one of a group of neurological conditions known as the... more...

GeneReviews: NBK1172

Clinical features from OMIM:

203450

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Search GEO for disease gene expression data for Alexander Disease.