IEMbase 0159: DPYD-related dihydropyrimidine dehydrogenase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 159 |
| Nosology | 16.1.01.01 |
| Gene | DPYD |
| External IDs | OMIM:274270; OMIM:612779; ORPHA:1675 |
| Generated mapping | UNMAPPED |
| Candidate DisMech targets | None |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as DPYD-related dihydropyrimidine dehydrogenase deficiency, with alternate labels thymine-uraciluria and DPD. Treatability is marked unknown.
The biochemical rows show decreased WBC dihydropyrimidine dehydrogenase and increased 5-OH-methyluracil, plasma and urinary thymine, and plasma and urinary uracil. The clinical rows are variable and include cerebral atrophy, cerebellar white-matter MRI abnormalities, epilepsy/seizures, abnormal eye movements, nystagmus, optic atrophy, coloboma, microcephaly, feeding difficulties, hypotonia, hypertonia, hyperactivity, psychomotor retardation, intellectual disability, autism, and severe 5-fluorouracil toxicity in affected individuals and heterozygotes.
DisMech phenotype coverage
There is no local standalone DPYD/dihydropyrimidine dehydrogenase deficiency entry.
Chemotherapy_Induced_Diarrhea.yaml contains DPYD pharmacogenomic
susceptibility to fluoropyrimidine toxicity and DPYD-guided dosing context.
That is clinically relevant to the IEMbase 5-fluorouracil toxicity rows, but
it is not the inherited DPYD deficiency disease target and does not model the
thymine/uracil biochemical phenotype or neurodevelopmental presentation.
Concordance and completeness
Judgement: true local gap with pharmacogenetic overlap.
DisMech currently covers DPYD as a modifier of fluoropyrimidine toxicity, not as a monogenic inborn error of pyrimidine catabolism. The IEMbase disease has a distinct biochemical signature, clinical neurodevelopmental spectrum, and toxicity-risk implication that should not be collapsed into chemotherapy-induced diarrhea.
Curation actions
- Leave IEMbase 159 unmapped for now.
- Future curation should decide whether DPYD deficiency is represented as a metabolic disease entry, a pharmacogenetic/toxicity entry, or both with clear scope boundaries.
- If curated, include WBC DPD activity, thymine/uracil accumulation, neurodevelopmental features, and severe fluoropyrimidine toxicity risk.