ORPHA:395

Homocystinuria due to methylene tetrahydrofolate reductase deficiency

high confidenceDisorder

Also known as: MTHFR deficiency · Methylene tetrahydrofolate reductase deficiency

Publications

791

89.8th percentile

Trials

Interventional, condition-specific

Researchers

1,186

Distinct authors in sample

Gene link

MTHFR

Definitive

Readiness

3/6

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.”

3/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

Gene identifiedPresent
Definitive — MTHFR
LiteraturePresent
791 matched papers (476 in last 10 years) Source
Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
Animal modelNot checked
Not yet enriched from Monarch / Alliance
Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
Interventional trialPresent
10 matched on ClinicalTrials.gov (2 recruiting in sample)

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.

MTHFR

Phenotypes (Monarch / HPO)

Not enriched in this build — Monarch phenotype joins were not run for this record.

Animal models (Monarch / Alliance)

Not enriched in this build.

Literature

Is anyone studying this?

791

791 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=5449) is 41.

791 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).

476 in the last 10 years · high confidence · 89.8th percentile (publications denominator)

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?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

01
Huemer M10 papers · 2026
Division of Metabolism and Children's Research Center, University Childrens' Hospital Zürich, Zurich, Switzerland.
Papers in Europe PMC
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
03
Caudill MA8 papers · 2026
Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Papers in Europe PMC
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
05
Schiff M7 papers · 2026
Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, France.
Papers in Europe PMC
06
Gleich F6 papers · 2024
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.
Papers in Europe PMC
07
Kölker S6 papers · 2024
Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.
Papers in Europe PMC
08
Benoist JF5 papers · 2024
Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, France.
Papers in Europe PMC
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
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?

interventional trials for this specific condition

10 interventional trials matched this specific condition name; 2 currently recruiting in our sample. 13 trials are registered for homocystinuria, the broader category — shown separately because they may or may not enrol this specific subtype.

Data as of 27 July 2026

10 interventional trials — more than 73% of diseases in the trials denominator have none at all (5114 of 7003; this disease is at the 91.7th percentile).

high confidence · 91.7th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

10 interventional trials matched after quoted-phrase search and title/condition post-filter.

NCT04974138·RECRUITING·China Stroke Primary Prevention Trial 2 for Participants With H-type Hypertension and MTHFR 677 CC/CT Genotype (CSPPT2-CC/CT)
Conditions: Hypertension · MTHFR 677 CC or CT Genotype · Elevated Plasma Homocysteine (Hcy≥10µmol/L) · Insufficient Plasma Folate Levels (<12ng/mL)·Matched via name phrase
NCT04974151·RECRUITING·China Stroke Primary Prevention Trial 2 for Participants With Hypertension and MTHFR 677 TT Genotype
Conditions: Hypertension · MTHFR 677 TT Genotype·Matched via name phrase

Broader category: homocystinuria

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

NCT06247085·RECRUITING·A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care Treatment
Conditions: Homocystinuria·Matched via name phrase
NCT06622577·NOT YET RECRUITING·The Effect of Dietary Management and Cysteine Supplementation on Growth Parameters and Biochemical Control for Pediatric Qatari Patients Affected with Classical B6 Non-responsive Homocystinuria.
Conditions: Classical Homocystinuria·Matched via name phrase
NCT06431893·ENROLLING BY INVITATION·A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)
Conditions: Homocystinuria·Matched via name phrase

Observational and natural-history studies

11 observational studies match 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

Where to find support

We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:

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"

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" OR "MTHFR"

Recall-expansion terms: MTHFR

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 10 interventional · 11 observational · 0 expanded access. Only interventional studies enter the trial headline.

Parent-category trials query:

"homocystinuria"

Query health: ok — strategies attempted: phrase, recall-expansion; with hits: phrase, recall-expansion

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

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