KEGG   DISEASE: H00869Help
Entry
H00869                      Disease                                

Name
Leukoencephalopathy with vanishing white matter;
Vanishing white matter disease;
Childhood ataxia with diffuse central nervous system hypomyelination (CACH);
Cree leukoencephalopathy (CLE)
Description
Leukoencephalopathy with vanishing white matter (VWM), also referred to as childhood ataxia with diffuse central nervous system hypomyelination (CACH), is one of the most prevalent inherited childhood disorders of cerebral white matter. This autosomal recessive progressive neurological disorder usually begins in early childhood, but a wide spectrum of clinical severity is now recognized from fatal infantile forms such as Cree leukoencephalopathy to mild later-onset forms associated with ovarian failure. The principal findings are cerebellar ataxia and spasticity with relative preservation of mental abilities. The course is typically relapsing-remitting with progressive neurological deterioration leading to death in the second decade of life. Nearly all patients have mutations in any of the 5 genes encoding the eukaryotic translation initiation factor eIF2B. Mutated eIF2B could impair the ability of cells to regulate protein synthesis, especially under conditions of cell stress. Reduced levels of eIF2 activity as occurs in VWM may lead to activation of the unfolded protein response inducing both prosurvival and proapoptotic signals affecting oligodendrocytes and astrocytes in particular.
Category
Nervous system disease
BRITE hierarchy
Pathway
RNA transport
Gene
EIF2B1 [HSA:1967] [KO:K03239]
EIF2B2 [HSA:8892] [KO:K03754]
EIF2B3 [HSA:8891] [KO:K03241]
EIF2B4 [HSA:8890] [KO:K03680]
EIF2B5 [HSA:8893] [KO:K03240]
Other DBs
ICD-10: 
MeSH: 
OMIM: 
Reference
PMID:17414998 (description, gene)
  Authors
Lyon G, Fattal-Valevski A, Kolodny EH
  Title
Leukodystrophies: clinical and genetic aspects.
  Journal
Top Magn Reson Imaging 17:219-42 (2006)
Reference
PMID:16807905 (description, gene)
  Authors
Pronk JC, van Kollenburg B, Scheper GC, van der Knaap MS
  Title
Vanishing white matter disease: a review with focus on its genetics.
  Journal
Ment Retard Dev Disabil Res Rev 12:123-8 (2006)
Reference
PMID:20838246 (description, gene)
  Authors
Bugiani M, Boor I, Powers JM, Scheper GC, van der Knaap MS
  Title
Leukoencephalopathy with vanishing white matter: a review.
  Journal
J Neuropathol Exp Neurol 69:987-96 (2010)

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