Disease Directory Vanishing White Matter Disease
Neurological

Vanishing White Matter Disease

Also known as: VWM, childhood ataxia with central nervous system hypomyelination, CACH syndrome, eIF2B deficiency

Prevalence

1-9 per 100,000 (Orphanet)

Onset

Infantile, Childhood, Adolescent, Adult

Type

Autosomal recessive genetic

Gene

EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5

About Vanishing White Matter Disease

Vanishing white matter disease (VWM) is caused by mutations in any of the five EIF2B subunit genes encoding eukaryotic initiation factor 2B, which regulates the integrated stress response. The characteristic feature is progressive rarefaction and cystic degeneration of cerebral white matter that appears nearly absent on MRI. Stress triggers (fever, infection, minor head trauma) cause episodic neurological crises with rapid deterioration, and the disease is often fatal in childhood for early-onset forms.

Common Clinical Features

Progressive cerebellar ataxia Spasticity Episodic deterioration triggered by stress White matter cystic changes on MRI Epilepsy Optic atrophy Premature ovarian failure (females)

Clinical Trial Eligibility Tips

What to know before applying to Vanishing White Matter Disease trials.

EIF2B subunit gene sequencing and protein activity assay are required for diagnosis — document which EIF2B subunit is affected

Brain MRI pattern (diffuse white matter signal change with cystic change and characteristic spectroscopy) is a required enrollment document

Fever and infection prevention protocol during trial participation is critical — trial sites must have VWM emergency management plans

Premature ovarian failure in female patients is a distinct manifestation that may qualify for separate reproductive health sub-studies

Patient Resources

Patient Organization

United Leukodystrophy Foundation

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Natural History Registry

Global Leukodystrophy Initiative (GLIA)

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Orphanet

European reference resource for rare diseases (ORPHA:135)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting Vanishing White Matter Disease trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Vanishing White Matter Disease. Updated daily.

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