IEMbase 0042: ALDH18A1-related pyrroline-5-carboxylate synthetase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 42 |
| Nosology | 1.7.14.01 |
| Gene | ALDH18A1 |
| External IDs | OMIM:138250; OMIM:219150 |
| Generated mapping | AMBIGUOUS by alias_exact:spg9a |
| Candidate DisMech targets | ALDH18A1_De_Barsy_Spectrum.yaml; ALDH18A1_De_Barsy_Spectrum.yaml#SPG9A |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this record as autosomal dominant ALDH18A1-related pyrroline-5-carboxylate synthetase deficiency, explicitly tied to SPG9A. The biochemical signal is low-to-normal plasma arginine, citrulline, ornithine, and proline.
The clinical pattern is SPG9A-facing rather than cutis-laxa-facing. IEMbase marks spastic paraparesis/paraplegia/tetraplegia, pyramidal signs, hypertonia, gait disturbance, muscle weakness, muscle wasting, dysarthria, pes cavus, spinal cord atrophy, cataract, gastroesophageal reflux, vomiting, growth retardation, short stature, and variable intellectual disability or global developmental delay. Cutis laxa, wrinkly skin, and joint laxity are explicitly normal in the cached phenotype table.
DisMech phenotype coverage
The generated ambiguity is understandable but resolvable. The parent file
ALDH18A1_De_Barsy_Spectrum.yaml is the correct local container, and the
SPG9A subtype is the best canonical target for this IEMbase record.
DisMech models ALDH18A1-related P5CS deficiency as a spectrum containing dominant SPG9A, recessive SPG9B, and ARCL3A/De Barsy presentations. It already captures autosomal dominant SPG9A, dominant-negative P5CS oligomer disruption, impaired proline and ornithine biosynthesis, low plasma proline, ornithine, citrulline, and arginine, spastic paraplegia, cataracts, gastroesophageal reflux, preserved or milder cognition in SPG9A, and the broader spectrum mechanisms involving antioxidant metabolism, extracellular-matrix changes, and neurodevelopmental/corticospinal involvement.
Concordance and completeness
Judgement: map this IEMbase record to
ALDH18A1_De_Barsy_Spectrum.yaml#SPG9A, with the parent spectrum retained as
context. The ambiguity is caused by the same alias matching both the file-level
spectrum and the subtype.
Concordance is high for the gene, inheritance, P5CS mechanism, amino-acid profile, spastic paraplegia, cataract, and reflux. IEMbase adds more granular SPG9A phenotype detail, including dysarthria, gait disturbance, pes cavus, muscle wasting/weakness, spinal cord atrophy, vomiting, pyramidal signs, and explicit absence of cutis laxa/wrinkly skin/joint laxity. DisMech is stronger for mechanism and for placing SPG9A relative to SPG9B and ARCL3A.
Curation actions
- Prefer the subtype mapping
ALDH18A1_De_Barsy_Spectrum.yaml#SPG9Afor this record. - Consider adding IEMbase's granular SPG9A features to the subtype if supported: dysarthria, gait disturbance, pes cavus, muscle wasting/weakness, spinal cord atrophy, vomiting, and pyramidal signs.
- Preserve subtype boundaries: IEMbase ID 42 is not the cutis laxa/De Barsy presentation despite sharing ALDH18A1 and P5CS deficiency biology.