IEMbase 0073: DHFR-related dihydrofolate reductase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 73 |
| Nosology | 21.8.05.01 |
| Gene | DHFR |
| External IDs | OMIM:126060 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | Best fuzzy candidate Tetrahydrobiopterin_Deficiency.yaml#DHPR Deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive DHFR-related dihydrofolate reductase deficiency, with alternate labels megaloblastic anemia due to DHFR deficiency and DHFRD. Treatability is marked yes.
The characteristic biochemical signal includes abnormal CSF 5-methyltetrahydrofolic acid, abnormal plasma folate, abnormal blood hemoglobin, and abnormal plasma LDH. Additional rows include urinary FIGLU, plasma homocysteine, urinary methylmalonic acid, urinary orotic acid, CSF BH4, and CSF biogenic amine metabolites.
Characteristic clinical rows include megaloblastic anemia and delayed myelination. Additional clinical rows include ataxia, cerebral atrophy on MRI, epilepsy, abnormal eye movements, failure to thrive, microcephaly, oculogyric crisis, and pancytopenia. The treatment row is folinic acid.
DisMech phenotype coverage
No valid local DisMech target was found for DHFR-related human dihydrofolate reductase deficiency.
The best fuzzy candidate, Tetrahydrobiopterin_Deficiency.yaml#DHPR Deficiency,
is a false positive. DHPR deficiency is QDPR-related dihydropteridine reductase
deficiency in BH4 regeneration. DHFR deficiency is a distinct folate-cycle
enzyme defect. The local bacterial folate-synthesis module and antimicrobial
entries that mention DHFR are drug-mechanism contexts, not human DHFR deficiency.
Concordance and completeness
Judgement: true local gap.
This is a treatable folate-metabolism disorder with a hematologic and neurodevelopmental phenotype. It should not be mapped to DHPR/QDPR deficiency or to antimicrobial DHFR target modules, despite the close acronyms and folate terminology.
Curation actions
- Keep this IEMbase record unmapped for now.
- Add a future standalone DHFR deficiency entry.
- If curated later, prioritize folate-cycle enzyme deficiency, megaloblastic anemia/pancytopenia, CSF 5-MTHF and folate markers, delayed myelination and epilepsy, and folinic-acid treatment.