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ORPHA:395

Homocystinuria due to methylene tetrahydrofolate reductase deficiency

low confidenceDisorder

Also known as: MTHFR deficiency · Methylene tetrahydrofolate reductase deficiency

Publications

21,650

Trials

0

Interventional, condition-specific

Researchers

1,186

Distinct authors in sample

Gene link

MTHFR

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Homocystinuria due to methylene tetrahydrofolate reductase (MTHFR) deficiency is a disorder characterised by neurological manifestations.

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 (2)

homocystinuria due to methylene tetrahydrofolate reductase deficiency · methylene tetrahydrofolate reductase deficiency

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 specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Definitive — MTHFR

  2. LiteraturePresent

    21,650 matched papers (11,064 in last 10 years) Source

  3. Phenotype characterisedPresent

    61 HPO annotations (e.g. Atypical behavior; Gait disturbance; Morphological central nervous system abnormality) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

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

  6. Interventional trialPartial

    None under the specific name; 13 for broader category homocystinuria

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 (MTHFR).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

61

Associated phenotypes · MONDO:0009353

  • Atypical behavior
  • Gait disturbance
  • Morphological central nervous system abnormality
  • Lower limb spasticity
  • Homocystinuria

Showing 5 of 61 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

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

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

21,650

21,650 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

21,650 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).

11,064 in the last 10 years · low confidence

Phrase hits: 791 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,186

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
    Huemer M10 papers · 2026

    Division of Metabolism and Children's Research Center, University Childrens' Hospital Zürich, Zurich, Switzerland.

    Papers in Europe PMC
  2. 02
    Rozen R9 papers · 2025

    Departments of Human Genetics and Pediatrics, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.

    Papers in Europe PMC
  3. 03
    Caudill MA8 papers · 2026

    Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.

    Papers in Europe PMC
  4. 04
    Kožich V7 papers · 2026

    Institute of Inherited Metabolic Disorders, Charles University-First Faculty of Medicine and General University Hospital, Prague, Czech Republic.

    Papers in Europe PMC
  5. 05
    Schiff M7 papers · 2026

    Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, France.

    Papers in Europe PMC
  6. 06
    Gleich F6 papers · 2024

    Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.

    Papers in Europe PMC
  7. 07
    Kölker S6 papers · 2024

    Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.

    Papers in Europe PMC
  8. 08
    Benoist JF5 papers · 2024

    Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, France.

    Papers in Europe PMC
  9. 09
    Bottiglieri T5 papers · 2025

    Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, TX, USA.

    Papers in Europe PMC
  10. 10
    Christensen KE5 papers · 2025

    Departments of Human Genetics and Pediatrics, Research Institute of the McGill University Health Center, McGill University, Montreal, QC H4A 3J1, Canada.

    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. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial. 13 trials are registered for homocystinuria, the broader category — shown separately because they may or may not enrol this specific subtype.

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.

13 interventional trials matched homocystinuria, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: homocystinuria

13

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Worth raising with a clinician. How we count trials.

Recruiting under the broader category

Observational and natural-history studies

1 observational study matches this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

None of the matched observational studies is currently listed as recruiting.

Open the complete matched search on ClinicalTrials.gov

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 Homocystinuria due to methylene tetrahydrofolate reductase deficiency — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Homocystinuria as a category (Group 2), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 2 — long-term / lifelong lower-cost interventions

NPRD envisages State Government support for dietary formulae, hormones, and other lower-cost interventions. This is a different route from the central CoE ₹50 lakh pathway; ask your state health department and a CoE which channel applies.

Central CoE funding may also apply depending on current rules — confirm with a notified Centre of Excellence. Do not assume the ₹50 lakh ceiling covers Group 2 by default. Verify

Centres of Excellence (15)
  • All India Institute of Medical Sciences (AIIMS) — New Delhi, Delhi
  • Maulana Azad Medical College — New Delhi, Delhi
  • Sanjay Gandhi Post Graduate Institute of Medical Sciences — Lucknow, Uttar Pradesh
  • Post Graduate Institute of Medical Education and Research (PGIMER) — Chandigarh, Chandigarh
  • Centre for DNA Fingerprinting & Diagnostics with Nizam’s Institute of Medical Sciences — Hyderabad, Telangana
  • King Edward Memorial Hospital — Mumbai, Maharashtra
  • Institute of Post-Graduate Medical Education and Research (IPGMER) — Kolkata, West Bengal
  • Centre for Human Genetics with Indira Gandhi Hospital — Bengaluru, Karnataka
  • Institute of Child Health and Hospital for Children (ICH & HC) — Chennai, Tamil Nadu
  • All India Institute of Medical Sciences (AIIMS) — Jodhpur, Rajasthan
  • Sree Avittam Thirunal Hospital (SAT), Government Medical College — Thiruvananthapuram, Kerala
  • All India Institute of Medical Sciences (AIIMS) — Bhopal, Madhya Pradesh
  • Regional Institute of Medical Sciences (RIMS) — Imphal, Manipur
  • All India Institute of Medical Sciences (AIIMS) — Patna, Bihar
  • Assam Medical College & Hospital — Dibrugarh, Assam

Voluntary contributions / crowdfunding (separate from CoE funding): https://rarediseases.mohfw.gov.in/

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.

("Homocystinuria due to methylene tetrahydrofolate reductase deficiency" OR "MTHFR deficiency" OR "Methylene tetrahydrofolate reductase deficiency") OR ("MTHFR" OR "MTHFR syndrome" OR "MTHFR-related")

Run this search on Europe PMC

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

"Homocystinuria due to methylene tetrahydrofolate reductase deficiency" OR "MTHFR deficiency" OR "Methylene tetrahydrofolate reductase deficiency"

Study-type breakdown: 0 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"homocystinuria"

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

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (21650) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-26T13:42:17.381Z