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ORPHA:319651

Constitutional megaloblastic anemia with severe neurologic disease

low confidenceDisorder

Also known as: DHFR deficiency · Dihydrofolate reductase deficiency

Query health: suspect — Only one of 2 strategies returned hits (phrase).

Publications

20,460

Trials

0

Interventional, condition-specific

Researchers

605

Distinct authors in sample

Gene link

DHFR

Definitive

Readiness

4/6

Stages with a signal

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (1)

dihydrofolate 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 — DHFR

  2. LiteraturePresent

    20,460 matched papers (9,265 in last 10 years) Source

  3. Phenotype characterisedPresent

    23 HPO annotations (e.g. Ataxia; Hepatomegaly; Decreased CSF 5-methyltetrahydrofolate concentration) 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; 1 for broader category megaloblastic anemia

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 (DHFR).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

23

Associated phenotypes · MONDO:0013456

  • Ataxia
  • Hepatomegaly
  • Decreased CSF 5-methyltetrahydrofolate concentration
  • Megaloblastic anemia
  • Increased circulating lactate dehydrogenase concentration

Showing 5 of 23 — 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?

20,460

20,460 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.

20,460 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).

9,265 in the last 10 years · low confidence

Phrase hits: 123 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

605

Distinct author names in 123 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
    Cai H16 papers · 2026

    Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.

    Papers in Europe PMC
  2. 02
    Zhang Y13 papers · 2026

    Division of Molecular Medicine, Department of Anesthesiology, Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.

    Papers in Europe PMC
  3. 03
    Youn JY8 papers · 2025

    Division of Molecular Medicine, Cardiovascular Research Laboratories, Departments of Anesthesiology and Medicine, David Geffen School of Medicine, University of California Los Angeles, 650 Charles E Young Drive, Los Angeles, CA 90095, USA.

    Papers in Europe PMC
  4. 04
    Huang K6 papers · 2026

    Division of Molecular Medicine, Department of Anesthesiology, Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.

    Papers in Europe PMC
  5. 05
    Siu KL6 papers · 2021

    Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.

    Papers in Europe PMC
  6. 06
    Chasin LA5 papers · 1994
    Papers in Europe PMC
  7. 07
    Ferreira CR5 papers · 2023

    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

    Papers in Europe PMC
  8. 08
    Li Q5 papers · 2021

    Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA.

    Papers in Europe PMC
  9. 09
    Blau N4 papers · 2023

    Division of Metabolism, University Children's Hospital, Zürich, Switzerland. Electronic address: nenad.blau@kispi.uzh.ch.

    Papers in Europe PMC
  10. 10
    Gao L4 papers · 2012

    Division of Molecular Medicine, Cardiovascular Research Laboratories (CVRL), The Departments of Anesthesiology and Medicine, UCLA David Geffen School of Medicine, 650 Charles E Young Drive, BH550, Los Angeles, CA, 90095, USA.

    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). 1 trial are registered for megaloblastic anemia, 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.

1 interventional trial matched megaloblastic anemia, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: megaloblastic anemia

1

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.

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 2 · after dedupe 2 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 2 · dropped 0 · fetched 2026-07-30

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 (2)

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 Constitutional megaloblastic anemia with severe neurologic disease — 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.

("Constitutional megaloblastic anemia with severe neurologic disease" OR "DHFR deficiency" OR "Dihydrofolate reductase deficiency") OR (MESH:"Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency") OR ("DHFR" OR "DHFR syndrome" OR "DHFR-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency

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

"Constitutional megaloblastic anemia with severe neurologic disease" OR "DHFR deficiency" OR "Dihydrofolate reductase deficiency" OR "Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency"

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

Parent-category trials query:

"megaloblastic anemia"

Query health: suspect — strategies attempted: phrase, mesh; 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 (20460) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T13:31:25.444Z