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Updated: Aug 9, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Vanishing white matter disease
Marjo S van der Knaap1, Jan C Pronk, Gert C Scheper
1Department of Pediatrics and Child Neurology, VU University Medical Center, Amsterdam, Netherlands. ms.vanderknaap@vumc.nl
Abstract:
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.
Insights
Vanishing white matter disease (VWM), a common childhood neurological disorder, stems from defects in the protein synthesis factor eIF2B. This leads to progressive white matter loss, particularly affecting glial cells.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Vanishing white matter disease (VWM) is a prevalent inherited childhood leucoencephalopathy.
- It presents with chronic neurological deterioration, often starting in early childhood and characterized by cerebellar ataxia.
- VWM exhibits unique sensitivity to stressors like infections and trauma, potentially causing rapid decline and coma.
Purpose of the Study:
- To elucidate the underlying genetic defects and cellular mechanisms in Vanishing White Matter Disease.
- To understand the selective vulnerability of glial cells in VWM despite defects in a housekeeping gene.
- To explore the role of the unfolded-protein response in VWM pathophysiology.
Main Methods:
- Review of clinical phenotypes and diagnostic MRI findings in VWM patients.
- Analysis of the genetic basis involving subunits of eukaryotic translation initiation factor eIF2B.
- Investigation into the cellular impact on oligodendrocytes and astrocytes, and the unfolded-protein response.
Main Results:
- VWM is caused by mutations in genes encoding subunits of the eIF2B factor, crucial for protein synthesis.
- MRI scans are diagnostic, showing characteristic vanishing of cerebral white matter.
- Despite eIF2B being essential in all cells, oligodendrocytes and astrocytes are disproportionately affected.
Conclusions:
- Defects in eIF2B lead to Vanishing White Matter Disease, a severe leukoencephalopathy.
- The selective vulnerability of glial cells in VWM remains incompletely understood.
- Further research into the unfolded-protein response is critical for understanding VWM pathogenesis.
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