ALXDRD
MCID: ALX003
MIFTS: 63
|
Alexander Disease (ALXDRD)
Categories:
Eye diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
|
|
|
MalaCards integrated aliases for Alexander Disease:
Characteristics:Inheritance:
Alexander Disease Type Ii:
Autosomal dominant 58
Prevelance:
<1/1000000 (Japan) 58
Age Of Onset:
Alexander Disease:
All ages 58
Alexander Disease Type Ii:
Adolescent,Adult,Childhood 58
Alexander Disease Type I:
Infancy,Neonatal 58
OMIM®:57 (Updated 08-Dec-2022)
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 GeneReviews:24
Penetrance Penetrance appears to be nearly 100% in individuals with the infantile and juvenile forms [li et al 2002, messing & brenner 2003a, messing 2018]....
Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Anatomical: Neuronal diseases Eye diseases Mental diseases
ICD10:
32
ICD11:
33
Orphanet: 58
![]() ![]() External Ids:
|
MedlinePlus Genetics: 42 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 multiple system atrophy 1, 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 Signaling by Receptor Tyrosine Kinases and Neuroscience. The drug Metronidazole has been mentioned in the context of this disorder. Affiliated tissues include spinal cord, brain and eye, and related phenotypes are macrocephaly and intellectual disability NINDS: 52 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. GARD: 19 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. Symptoms of the infantile form include an enlarged brain and head, seizures, stiffness in the arms and/or legs, intellectual disability, and delayed physical development. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination. Alexander disease is caused by genetic changes in the GFAP gene. While this condition is inherited in an autosomal dominant fashion, most cases result from new genetic changes in the gene. OMIM®: 57 In decreasing order of frequency, 3 forms of Alexander disease (ALXDRD) 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) (Updated 08-Dec-2022) Orphanet 58 Alexander disease: 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. Alexander disease type i: An astrogliopathy and the most severe and common form of Alexander disease (AxD), presenting before the age of 4 and characterized by seizures, megalencephaly and developmental delay with progressive deterioration. Alexander disease type ii: An astrogliopathy and a form of Alexander disease (AxD) characterized by ataxia, bulbar symptoms, spastic paraparesis, palatal myoclonus, and autonomic symptoms. UniProtKB/Swiss-Prot: 73 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. Disease Ontology: 11 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. Wikipedia: 75 Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions... more...
GeneReviews:
NBK1172
|
Human phenotypes related to Alexander Disease:58 30 (show top 50) (show all 95)
Symptoms via clinical synopsis from OMIM®:57 (Updated 08-Dec-2022)Clinical features from OMIM®:203450 (Updated 08-Dec-2022)UMLS symptoms related to Alexander Disease:seizures; muscle spasticity GenomeRNAi Phenotypes related to Alexander Disease according to GeneCards Suite gene sharing:25
MGI Mouse Phenotypes related to Alexander Disease:45
|
Drugs for Alexander Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):
Interventional clinical trials:
Cochrane evidence based reviews: alexander disease |
Organs/tissues related to Alexander Disease:
MalaCards :
Spinal Cord,
Brain,
Eye,
Medulla Oblongata,
Bone Marrow,
Cortex,
Cerebellum
|
Articles related to Alexander Disease:(show top 50) (show all 572)
|
ClinVar genetic disease variations for Alexander Disease:5 (show top 50) (show all 137)
UniProtKB/Swiss-Prot genetic disease variations for Alexander Disease:73 (show top 50) (show all 62)
|
Search
GEO
for disease gene expression data for Alexander Disease.
|
Pathways related to Alexander Disease according to GeneCards Suite gene sharing:(show all 11)
|
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:
|
|