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ORPHA:135

CACH syndrome

low confidenceDisorder

Also known as: Childhood ataxia with diffuse central nervous system hypomyelination · Leukoencephalopathy with vanishing white matter · Myelinosis centralis diffusa

Publications

2,424

Trials

0

Interventional, condition-specific

Researchers

1,316

Distinct authors in sample

Gene link

EIF2B2

Strong

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A new leukoencephalopathy, the CACH syndrome (Childhood with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes ``foamy'' aspect.

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (3)

childhood ataxia with diffuse central nervous system hypomyelination · leukoencephalopathy with vanishing white matter · myelinosis centralis diffusa

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

4/6 stages with a signal

No matched interventional trial, but a gene association and an animal model are on record — often described as translation-ready / stalled at the clinical step.

  1. Gene identifiedPresent

    Strong — EIF2B2

  2. LiteraturePresent

    2,424 matched papers (827 in last 10 years) Source

  3. Phenotype characterisedPresent

    143 HPO annotations (e.g. Blindness; Macrocephaly; Cessation of head growth) Source

  4. Animal modelPresent

    14 genotype models (Danio rerio, Mus musculus) Source

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. Interventional trialNot found

    No matched interventional trial under our ClinicalTrials.gov rules

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (EIF2B2).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

143

Associated phenotypes · MONDO:0800448

  • Blindness
  • Macrocephaly
  • Cessation of head growth
  • Hypotonia
  • Decreased circulating progesterone

Showing 5 of 143 — open Monarch for the full list.

Animal models (Monarch / Alliance)

14

Model associations linked to this Mondo ID

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

1

Drugs / clinical candidates · MONDO_0800448

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

2,424

2,424 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

2,424 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

827 in the last 10 years · low confidence

Phrase hits: 252 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,316

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.

  1. 01
    Wu Y9 papers · 2026

    Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, New South Wales, Australia.

    Papers in Europe PMC
  2. 02
    Cach G7 papers · 2026

    Orthopaedic Surgery, Georgetown University School of Medicine, Washington, DC, USA.

    Papers in Europe PMC
  3. 03
    Jiang Y7 papers · 2026

    Department of Neurobiology, Capital Medical University, 10 You'an Men Wai, Xitoutiao, Beijing, 100069, China.

    Papers in Europe PMC
  4. 04
    Wang J7 papers · 2025

    Department of Pediatrics, Peking University First Hospital, Beijing, China.

    Papers in Europe PMC
  5. 05
    Zhang J7 papers · 2026

    Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou.

    Papers in Europe PMC
  6. 06
    Cach-Pérez MJ6 papers · 2025

    El Colegio de la Frontera Sur, Guineo, Second Section, Villahermosa 86280, Mexico.

    Papers in Europe PMC
  7. 07
    Tamay-Cach F5 papers · 2026

    Laboratorio de Investigación en Enfermedades Crónico Degenerativas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Ciudad de México 11340, Mexico.

    Papers in Europe PMC
  8. 08
    Zhang H5 papers · 2026

    Beijing Key Laboratory of Urban Underground Space Engineering, School of Civil and Resource Engineering, University of Science and Technology Beijing, Beijing 100083, China.

    Papers in Europe PMC
  9. 09
    Arellano-Mendoza MG4 papers · 2026

    Laboratorio de Investigación en Enfermedades Crónico Degenerativas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Ciudad de México 11340, Mexico. Electronic address: emi_monic@yahoo.com.

    Papers in Europe PMC
  10. 10
    Deng J4 papers · 2025

    Department of Pediatrics, Peking University First Hospital, Beijing, China.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

0

interventional trials for this specific condition

No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).

Data as of 11 September 2026 · last trial check 11 September 2026

No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.

low confidence · 38.6th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.

See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 1 · after dedupe 1 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 1 · dropped 0 · fetched 2026-07-29

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Uncertain / not reviewed (1)

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for CACH syndrome — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("CACH syndrome" OR "Childhood ataxia with diffuse central nervous system hypomyelination" OR "Leukoencephalopathy with vanishing white matter" OR "Myelinosis centralis diffusa") OR ("EIF2B2" OR "EIF2B2 syndrome" OR "EIF2B2-related" OR "CACH" OR "CACH-related")

Run this search on Europe PMC

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"CACH syndrome" OR "Childhood ataxia with diffuse central nervous system hypomyelination" OR "Leukoencephalopathy with vanishing white matter" OR "Myelinosis centralis diffusa"

Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase; with hits: phrase

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is short or not clearly distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (2424) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-26T12:34:30.421Z