IEMbase 0038: ALDH4A1-related pyrroline-5-carboxylate dehydrogenase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 38 |
| Nosology | 1.7.06.01 |
| Gene | ALDH4A1 |
| External IDs | OMIM:239510 |
| Generated mapping | UNMAPPED; best fuzzy candidate Pyruvate_Dehydrogenase_Deficiency.yaml |
| Candidate DisMech targets | none currently valid |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ALDH4A1 deficiency as pyrroline-5-carboxylate dehydrogenase deficiency, also called hyperprolinemia type 2. The biochemical signal is high plasma proline, high urinary proline, increased urinary pyrroline-5-carboxylate, variable-to-markedly increased urinary 4-hydroxyproline, and normal plasma 4-hydroxyproline.
The clinical signal is sparse and uncertain: possible febrile seizures, possible pharmacoresistant seizures, and possible intellectual disability. Treatability is marked yes, but no treatment rows are present in the cached record.
DisMech phenotype coverage
There is no current DisMech entry or subtype for ALDH4A1-related
hyperprolinemia type 2. The generated fuzzy candidate,
Pyruvate_Dehydrogenase_Deficiency.yaml, should be rejected. PDH deficiency is
a mitochondrial pyruvate-to-acetyl-CoA disorder with lactate/pyruvate
accumulation and neurodevelopmental disease, not a proline catabolism disorder
with elevated proline and P5C.
ALDH18A1-related P5CS deficiency is also not a match. It impairs proline and ornithine biosynthesis and tends toward low or low-normal proline, whereas ALDH4A1 deficiency blocks proline degradation and produces hyperprolinemia.
Concordance and completeness
Judgement: generated unmapped status is correct; the PDH candidate is a false positive.
IEMbase provides a biochemical target profile for future curation but only weak clinical signal. The most important distinction to preserve is hyperprolinemia type 2 with elevated P5C, not generic seizure disease and not ALDH18A1 P5CS deficiency.
Curation actions
- Do not map this record to PDH deficiency or ALDH18A1 deficiency.
- Consider future curation only if the proline-catabolism work package becomes a priority.
- If curated, anchor the entry on elevated plasma/urinary proline and urinary P5C, with seizures and intellectual disability treated as uncertain or variable clinical associations unless supported by stronger evidence.