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leukoencephalopathy with vanishing white matter 5 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

leukoencephalopathy with vanishing white matter 5

MONDO:0957873

Overview

GeneticsAutosomal recessive · EIF2B5 (chr 3)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Progressive neurologic deterioration and Decreased CSF asialotransferrin to transferrin ratio; and common findings: Megalencephaly and Coma. 8 total HPO annotations.

Organ System	Phenotype Count	Example Features
Muscles	1	Loss of ambulation

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

EIF2B5 encodes eukaryotic translation initiation factor 2B subunit epsilon (721 aa). Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit. Highest expression in Brain Cerebellar Hemisphere (71.5 TPM) and Brain Cerebellum (70.7 TPM).

Leukoencephalopathy with vanishing white matter 5 is caused by mutations in the EIF2B5 gene on chromosome 3.

EIF2B5 is classified as a druggable target with score 0.0.

GeneReviews

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

Childhood ataxia with central nervous system hypomyelination/ vanishing white matter (CACH/VWM) should be suspected in individuals with the following clinical, laboratory, and imaging findings.

Clinical findings

Source: GeneReviews — "Childhood Ataxia with Central Nervous System Hypomyelination/ Vanishing White Matter"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for leukoencephalopathy with vanishing white matter 5. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with childhood ataxia with central nervous system hypomyelination / vanishing white matter (CACH/VWM), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Close surveillance for several days following head trauma or major surgical procedure with anesthesia is indicated because neurologic deterioration (presumably stress related) may follow.

Source: GeneReviews — "Childhood Ataxia with Central Nervous System Hypomyelination/ Vanishing White Matter"

Phenotype severity distribution: 2 always present features, 2 common features.

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for leukoencephalopathy with vanishing white matter 5.

203 publications have been identified in PubMed for leukoencephalopathy with vanishing white matter 5. Kisho has analyzed 140 by research type. Research spans Basic Science / Preclinical (44%), Review / Meta-Analysis (19%), and Epidemiology / Natural History (12%).

Research Type	Count	% of Total
Laboratory research	61	44%

Data assembled from 7 of 12 sources · Last updated Sep 18, 2026, 5:00 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:620315

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

Differential Diagnosis

Table 2. Other Disorders Affecting the White Matter Diffusely During Childhood to Consider in the Differential Diagnosis of CACH/VWM

Disorder	Gene(s)	MOI	Distinguishing MRI findings
AARS2	AR	Extensive or diffuse cerebral WM changes; Involvement of the corpus callosum connecting lesions on both sides; Involvement of long descending tracts Childhood cerebral form of X-linked adrenoleukodystrophy	—
ABCD1	XL	Extensive or diffuse cerebral WM changes but, as a rule, no cystic degeneration Arylsulfatase A deficiency (metachromatic leukodystrophy)	ARSA
GFAP	AD	WM signal changes have a frontal predominance.; The cystic degeneration may affect the subcortical or deep WM.; Basal ganglia thalamic abnormalities are frequently present.; Contrast enhancement of characteristic structures often facilitates diagnosis.	HEPACAM
MLC1	ARAD1	Diffusely abnormal mildly swollen cerebral hemispheric WM that does not show signs of diffuse rarefaction or cystic degeneration; Subcortical cysts are almost always present in the anterior temporal area often in other regions.; Cysts are best seen on proton density FLAIR.	—
Mitochondrial leukoencephalopathies	See footnote 2.	ADARmt	MRI abnormalities may be similar to those seen in CACH/VWM, but WM cysts are typically well delineated (in contrast to CACH/VWM).; Prominent diffuse WM rarefaction cystic degeneration may be seen in mitochondrial disorders.
PLP1	XL	Diffuse hyperintensity of WM on T2-weighted images is also observed in leukodystrophies w/primary hypomyelination (e.g., PLP1-related disorders), but these disorders have a normal or nearly normal WM signal on T1-weighted images CT scan.	—
NOTCH3	AD	Consider these disorders in those w/adult-onset CACH/VWM; however, the early constant diffuse symmetric alteration of WM on MRI in eIF2B-related disorders is distinctive. Autosomal dominant leukodystrophy with autonomic disease	LMNB1
AD Acquired white matter disorders such as multiple sclerosis	See footnote 3.	See footnote 4. AD = autosomal dominant; AR = autosomal recessive; CACH/VWM = childhood ataxia with central nervous system / hypomyelination / vanishing white matter; MOI = mode of inheritance; mt = mitochondrial; WM = white matter; XL = X-linked 1.	—

Source: GeneReviews — "Childhood Ataxia with Central Nervous System Hypomyelination/ Vanishing White Matter"

Kisho

leukoencephalopathy with vanishing white matter 5

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Treatment of Manifestations

Prevention of Secondary Complications

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Guanabenz in vanishing white matter: towards mechanism-based disease modification.

Clinical and genetic characteristics of pediatric patients with vanishing white matter disease: a retrospective single-center study.

Genetic screening of EIF2B genes reveals mutation spectrum and predicted prevalence of vanishing white matter disease in Chinese population.

leukoencephalopathy with vanishing white matter 5

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Treatment of Manifestations

Prevention of Secondary Complications

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Guanabenz in vanishing white matter: towards mechanism-based disease modification.

Clinical and genetic characteristics of pediatric patients with vanishing white matter disease: a retrospective single-center study.

Genetic screening of EIF2B genes reveals mutation spectrum and predicted prevalence of vanishing white matter disease in Chinese population.