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constitutional megaloblastic anemia with severe neurologic disease - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

constitutional megaloblastic anemia with severe neurologic disease

MONDO:0013456

Also known as:DHFR deficiencydihydrofolate reductase deficiencymegaloblastic anaemia due to dihydrofolate reductase deficiency

Overview

GeneticsAutosomal recessive · DHFR (chr 5)

ResearchLimited published research (1 article)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Decreased CSF 5-methyltetrahydrofolate concentration and Larger than normal red blood cells (increased mean corpuscular volume); and common findings: Megaloblastic anemia, Elevated LDH (tissue damage marker) (increased circulating lactate dehydrogenase concentration), and Absence seizure with eyelid myoclonia. 23 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	6

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

DHFR encodes dihydrofolate reductase (187 aa). Catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate in a NADPH-dependent manner. Key enzyme in folate metabolism. Highest expression in Cells EBV-transformed lymphocytes (33.1 TPM) and Cells Cultured fibroblasts (17.8 TPM).

Constitutional megaloblastic anemia with severe neurologic disease is associated with mutations in the DHFR gene on chromosome 5.

The DHFR protein participates in E2F1:TFDP1,TFDP2:DHFR gene, DHFR gene expression is stimulated by E2F1, and Salvage - BH2 is reduced to BH4 by DHFR pathways.

DHFR is classified as a druggable target (Druggable Genome and Enzyme categories) with score 3.2.

Diagnosis

Genetic testing for DHFR is available. Testing is considered confirmatory for diagnosis.

Prognosis

Phenotype severity distribution: 2 always present features, 3 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

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.

No clinical trials have been registered for constitutional megaloblastic anemia with severe neurologic disease.

1 publication has been identified in PubMed for constitutional megaloblastic anemia with severe neurologic disease. Research spans Case Report / Case Series (100%).

Recent Publications

Wang D (2025). [PMID: 40752814](https://pubmed.ncbi.nlm.nih.gov/40752814/). *Neuroscience*. [Case Report / Case Series]

Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 5:34 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:613839

Orphanet

European rare disease database

Orphanet:319651

GARD

Genetic and Rare Diseases Info Center

GARD:11000

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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constitutional megaloblastic anemia with severe neurologic disease

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

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Questions for Your Care Team

Questions for Your Care Team

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