leukoencephalopathy with vanishing white matter
An autosomal recessive leukodystrophy (OMIM:603896) of childhood onset, characterised by progressive cerebellar ataxia, spasticity, variable optic atrophy and relatively preserved IQ. It is usually slowly progressive, but may rapidly progress if triggered by fever or head trauma.
Clinical variants include a severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba–Cree leukoencephalopathy and a milder form affecting females who survive to adolescence and exhibit ovarian dysfunction–ovarioleukodystrophy.
Molecular pathology Defects in EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5, which encodes subunits of eukaryotic translation initiation factor 2B–EIF2B, an essential regulator of protein synthesis, are a cause of leukodystrophy with vanishing white matter.
Image to the left is of an infant with leukoencephalopathy with vanishing white matter exhibiting developmental regression. Widespread T2 hyperintensities were present in the white matter and FLAIR imaging revealed cystic white matter (image courtesy of Dr. Ai Hoshino of Tokyo Metropolitan Neurological Hospital).
Synonyms CACH, CACH syndrome, childhood ataxia with central nervous system hypomyelination, childhood ataxia with central nervous system hypomyelinisation, CLE, Cree leukoencephalopathy, myelinosis centralis diffusa, ovarioleukodystrophy*, vanishing white matter leukodystrophy, vanishing white matter leukodystrophy with ovarian failure*, VWM
*These are linked to defects in EIF2B2, EIF2B4, EIF2B5