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leukoencephalopathy with vanishing white matter (CACH) - Clinical Profile, Genes & Research | Kisho | Kisho

Features include very common findings: Dysmyelinating leukodystrophy and Brain imaging abnormality; and common findings: Damage to the optic nerve (optic atrophy), Irritability, Seizure, and Spasticity and others. 55 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	19	Brain imaging abnormality, Irritability, Seizure
Muscles	7	Damage to the optic nerve (optic atrophy), Shrinkage of the cerebellum (cerebellar atrophy), Brain shrinkage (cerebral atrophy)
Digestive system	5	Hepatosplenomegaly, Pancreatitis, Vomiting
Eyes	4	Damage to the optic nerve (optic atrophy), Cataract, Blindness
Head and neck	2	Microcephaly, Progressive macrocephaly
Hormones	2	Primary amenorrhea, Secondary amenorrhea
Growth and development	2	Growth delay, Intrauterine growth retardation
Arms and legs	1	Limb ataxia
Kidneys and urinary system	1	Renal hypoplasia
Pregnancy and birth	1	Decreased fetal movement
Heart and blood vessels	1	Widened subarachnoid space

GeneReviews

Clinical Guidance

Childhood ataxia with central nervous system hypomyelination/ vanishing white matter (CACH/VWM) phenotypes range from a congenital or early-infantile form (onset age 1 year) to an early childhood-onset form (onset age 1 to 4 years), a late-childhood/juvenile-onset form (onset age 4 to 18 years), and an adult-onset form (onset ≥18 years . Both the childhood and juvenile forms have been observed in sibs; the infantile and juvenile/adult forms have never been observed within the same family . Neurology. The neurologic signs depend on the age of onset . In the congenital and early-infantile forms, the encephalopathy is severe, seizures are often a predominant clinical feature, and decline is rapid and followed quickly by death.

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

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"

GeneReviews

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.

Biomarker and diagnostic research for leukoencephalopathy with vanishing white matter has been reported in the published literature.

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. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for leukoencephalopathy with vanishing white matter, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for leukoencephalopathy with vanishing white matter. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor	Designated	Exclusivity End	Designation Status
Sodium ({(2S)-1,4-bis[2-(4-chloro-3- fluorophenoxy)acetamido]bicyclo[2.2.2]octan-2- yl}oxy)methyl hydrogen phosphate - 2-amino-2- (hydroxymethyl)propane-1,3-diol (1/1/1)	Sodium ({(2S)-1,4-bis[2-(4-chloro-3- fluorophenoxy)acetamido]bicyclo[2.2.2]octan-2- yl}oxy)methyl hydrogen phosphate - 2-amino-2- (hydroxymethyl)propane-1,3-diol (1/1/1)	Calico Life Sciences LLC	2022	—	Designated

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:

Brain MRI
Ophthalmologic examination
Neurologic examination
Physical therapy/occupational therapy assessment as needed
Consultation with a clinical geneticist and/or genetic counselor

Note: If an individual is diagnosed while asymptomatic, either because of an affected sib or as an incidental finding on exome sequencing, the above evaluations and the recommendations in should be applied.

Treatment of Manifestations

The following are appropriate:

Physical therapy and rehabilitation for motor dysfunction (mainly spasticity and ataxia)
Ankle-foot orthotics in individuals with hypotonia and weakness of ankle dorsiflexors
Anti-seizure medication for treatment of seizures and abnormalities of behavior and mood

GeneReviews

Clinical Guidance

Avoid the following:

Contact sports and other activities with a high risk of head trauma
Stressful emotional and physical situations (e.g., acute fright, fever and other causes of extreme temperatures, major surgery)

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

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

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

Clinical Trials

5 trials found

Explore Trials

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.

5 clinical trials registered, 3 recruiting. Interventions under study include drug therapy, other interventions, and biologic therapy. Pipeline includes 1 PHASE1, 1 EARLY_PHASE1, 1 NA. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT07272525](https://clinicaltrials.gov/study/NCT07272525)	Research Study for Single-Patient Treatment of Cree Leukoencephalopathy/Vanishing White Matter Disease	EARLY_PHASE1	McGill University Health Centre/Research Institute of the McGill University Health Centre	UNKNOWN
[NCT07300397](https://clinicaltrials.gov/study/NCT07300397)	Single Patient Investigational Treatment for Cree Leukoencephalopathy	NA	McGill University Health Centre/Research Institute of the McGill University Health Centre	ACTIVE_NOT_RECRUITING
[NCT03047369](https://clinicaltrials.gov/study/NCT03047369)	The Myelin Disorders Biorepository Project	—	Children's Hospital of Philadelphia	RECRUITING
[NCT05757141](https://clinicaltrials.gov/study/NCT05757141)	An Open-Label Exploratory Study of Fosigotifator in Participants With Vanishing White Matter Disease	PHASE1	Calico Life Sciences LLC	RECRUITING
[NCT03333200](https://clinicaltrials.gov/study/NCT03333200)	Longitudinal Study of Neurodegenerative Disorders	—	University of Pittsburgh	RECRUITING

159 publications have been identified in PubMed for leukoencephalopathy with vanishing white matter. Research spans Basic Science / Preclinical (43%), Review / Meta-Analysis (21%), and Case Report / Case Series (11%).

Research Type	Count	% of Total
Laboratory research	69	43%
Research summaries	33	21%
Patient case studies	17	11%
Disease patterns and progression	17	11%
Testing and diagnosis research	10	6%
New treatment approaches	8

Recent Publications

Guo J (2026). [PMID: 41533076](https://pubmed.ncbi.nlm.nih.gov/41533076/). *Inflamm Res*. [Basic Science / Preclinical]
Yang L (2026). [PMID: 40841755](https://pubmed.ncbi.nlm.nih.gov/40841755/). *Molecular psychiatry*. [Basic Science / Preclinical]
Sonner JK (2026). [PMID: 41540266](https://pubmed.ncbi.nlm.nih.gov/41540266/). *Nature immunology*. [Basic Science / Preclinical]
Komiyama S (2026). [PMID: 41512014](https://pubmed.ncbi.nlm.nih.gov/41512014/). *Proceedings of the National Academy of Sciences of the United States of America*. [Clinical Trial Publication]
Azimzadeh M (2026). [PMID: 41418666](https://pubmed.ncbi.nlm.nih.gov/41418666/). *Biomed Pharmacother*. [Basic Science / Preclinical]
Miura Y (2026). [PMID: 42156040](https://pubmed.ncbi.nlm.nih.gov/42156040/). *Brain Nerve*. [Review / Meta-Analysis]
Park Y (2026). [PMID: 41109658](https://pubmed.ncbi.nlm.nih.gov/41109658/). *Experimental neurology*. [Review / Meta-Analysis]
An X (2026). [PMID: 41271597](https://pubmed.ncbi.nlm.nih.gov/41271597/). *Advanced science (Weinheim, Baden-Wurttemberg, Germany)*. [Basic Science / Preclinical]
Goodall LS (2026). [PMID: 41498480](https://pubmed.ncbi.nlm.nih.gov/41498480/). *Journal of the American College of Cardiology*. [Review / Meta-Analysis]
Marten LM (2026). [PMID: 41177236](https://pubmed.ncbi.nlm.nih.gov/41177236/). *Free Radic Biol Med*. [Basic Science / Preclinical]

Kisho

leukoencephalopathy with vanishing white matter

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Treatment of Manifestations

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Prevention of Secondary Complications

Latest News & Developments

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

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Treatment of Manifestations

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Prevention of Secondary Complications

Latest News & Developments

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.