Alexander Disease (ALXDRD)

External Ids:

Disease Ontology 12 DOID:4252 OMIM 58 203450 KEGG 38 H00065 MeSH 45 D038261 NCIt 51 C84545 SNOMED-CT 69 81854007 MESH via Orphanet 46 D038261

ICD10 via Orphanet 35 E75.2 UMLS via Orphanet 75 C0270726 Orphanet 60 ORPHA363717 ORPHA363722 ORPHA58 MedGen 43 C0270726 SNOMED-CT via HPO 70 111266001 11538006 11934000 123527003 128613002 14648003 14760008 161857006 16932000 17944005 18963009 193093009 19410003 20301004 21061000119107 221360009 22325002 225595004 228156007 230745008 24184005 246545002 247578003 248062006 249710008 24982008 26079004 263681008 271700006 27272007 274521009 288939007 312230002 312894000 313307000 35489007 36440009 364538006 36649002 38341003 386689009 397790002 398151007 398152000 400179000 40739000 40930008 409623005 414564002 415690000 415691001 432788009 45007003 45170000 47004009 5102002 52613005 563001 609225004 61960001 64217002 65958008 72042002 73211009 73430006 78441005 78667006 8011004 84757009 85102008 90145001 91138005 91175000 95281009 95427009 95666008 more UMLS 74 C0270726 C2930798

NINDS : ⁵⁵ 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 aceruloplasminemia, 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 Cytoskeleton remodeling Neurofilaments and ATM Signaling Network in Development and Disease. Affiliated tissues include brain, eye and cortex, 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.

Genetics Home Reference : ²⁶ 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 : ⁵⁴ 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 : ⁵⁸ 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 : ⁷⁶ 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 : ⁷⁷ Alexander disease is one of a group of neurological conditions known as the leukodystrophies, which are... more...

GeneReviews: NBK1172

Clinical features from OMIM:

203450

Search NIH Clinical Center for Alexander Disease

Search GEO for disease gene expression data for Alexander Disease.