KEGG   DISEASE: Leukoencephalopathy with vanishing white matterHelp
H00869                      Disease                                

Leukoencephalopathy with vanishing white matter;
Vanishing white matter disease;
Childhood ataxia with diffuse central nervous system hypomyelination (CACH);
Cree leukoencephalopathy (CLE)
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.
Nervous system disease; Congenital disorder of metabolism
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00869  Leukoencephalopathy with vanishing white matter
 Congenital disorders of metabolism
  Congenital disorders of lipid/glycolipid metabolism
   H00869  Leukoencephalopathy with vanishing white matter
Human diseases in ICD-10 classification [BR:br08403]
 4. Endocrine, nutritional and metabolic diseases (E00-E90)
  E70-E90  Metabolic disorders
   E75  Disorders of sphingolipid metabolism and other lipid storage disorders
    H00869  Leukoencephalopathy with vanishing white matter
BRITE hierarchy
hsa03013  RNA transport
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: E75.2
MeSH: D056784
OMIM: 603896
PMID:17414998 (description, gene)
Lyon G, Fattal-Valevski A, Kolodny EH
Leukodystrophies: clinical and genetic aspects.
Top Magn Reson Imaging 17:219-42 (2006)
PMID:16807905 (description, gene)
Pronk JC, van Kollenburg B, Scheper GC, van der Knaap MS
Vanishing white matter disease: a review with focus on its genetics.
Ment Retard Dev Disabil Res Rev 12:123-8 (2006)
PMID:20838246 (description, gene)
Bugiani M, Boor I, Powers JM, Scheper GC, van der Knaap MS
Leukoencephalopathy with vanishing white matter: a review.
J Neuropathol Exp Neurol 69:987-96 (2010)

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