Vanishing white matter disease.
Vanishing white matter disease (VWM) is one of the most prevalent inherited childhood leucoencephalopathies. The classical phenotype is characterised by early childhood onset of chronic neurological deterioration, dominated by cerebellar ataxia. VWM is unusual because of its clinically evident sensitivity to febrile infections, minor head trauma, and acute fright, which may cause rapid neurological deterioration and unexplained coma. Most patients die a few years after onset. The phenotypic variation is extremely wide, including antenatal onset and early demise and adult-onset, slowly progressive disease. MRI findings are diagnostic in almost all patients and are indicative of vanishing of the cerebral white matter. The basic defect of this striking disease resides in either one of the five subunits of eukaryotic translation initiation factor eIF2B. eIF2B is essential in all cells of the body for protein synthesis and its regulation under different stress conditions. Although the defect is in housekeeping genes, oligodendrocytes and astrocytes are predominantly affected, whereas other cell types are surprisingly spared. Recently, undue activation of the unfolded-protein response has emerged as important in the pathophysiology of VWM, but the selective vulnerability of glia for defects in eIF2B is poorly understood.
van der Knaap
Marjo S
MS
Department of Pediatrics and Child Neurology, VU University Medical Center, Amsterdam, Netherlands. ms.vanderknaap@vumc.nl
Pronk
Jan C
JC
Scheper
Gert C
GC
D017668:Age of Onset; D001927:Brain Diseases / Q000235:genetics / Q000503:physiopathology*; D002524:Cerebellar Ataxia / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D020717:Eukaryotic Initiation Factor-2B / Q000235:genetics / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D010641:Phenotype; D011379:Prognosis; D017510:Protein Folding; D013315:Stress, Psychological
D020717:Eukaryotic Initiation Factor-2B