IEMbase 0395: ALDH18A1-related Delta-1-pyrroline-5-carboxylate synthase deficiency, cutis laxa phenotype
Scope
| Field | Value |
|---|---|
| IEMbase ID | 395 |
| Nosology | 1.7.01.01 |
| Gene | ALDH18A1 |
| External IDs | OMIM:219150; ORPHA:90348 |
| Generated mapping | MAPPED; ALDH18A1_De_Barsy_Spectrum.yaml |
| Candidate DisMech targets | ALDH18A1_De_Barsy_Spectrum.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ALDH18A1-related P5CS deficiency with cutis laxa phenotype, also listed as autosomal recessive cutis laxa type 3A, De Barsy syndrome ALDH18A1-associated, cutis laxa autosomal recessive 3A, cutis laxa autosomal dominant 3, ARCL3A, ADCL3, and P5CSD. Inheritance is listed as both autosomal dominant and autosomal recessive.
Characteristic rows include cutis laxa, wrinkly skin, cataract, developmental delay, microcephaly, progeroid appearance, and mitral valvulitis. Additional rows include feeding difficulties, failure to thrive, short stature, joint laxity/contractures, hip dislocation, osteoporosis/osteopenia, pes planus, rhizomelia, tortuous blood vessels, hernias, corneal clouding, dystonia, seizures, corpus-callosum and white-matter abnormalities, sparse hair, and Wormian bones. Biochemical rows include low-to-normal arginine, citrulline, ornithine, proline, brain creatine, and normal-to-increased blood ammonia.
DisMech phenotype coverage
The generated mapping to ALDH18A1_De_Barsy_Spectrum.yaml is correct. Local
DisMech intentionally models the ALDH18A1 spectrum across dominant SPG9A,
recessive SPG9B, and ARCL3A/De Barsy presentations. It covers P5CS function in
proline and ornithine biosynthesis, reduced plasma proline/ornithine/
citrulline/arginine, hyperammonemia, cutis laxa or wrinkled skin, cataracts,
short stature/failure to thrive, microcephaly, developmental delay, connective
tissue changes, and semidominant inheritance.
Local coverage is stronger for mechanism and spectrum placement. IEMbase is especially useful for granular ARCL3A skeletal, ocular, vascular, and brain phenotype prompts.
Concordance and completeness
Judgement: correct mapping with high concordance.
The resources agree on ALDH18A1/P5CS identity, dominant and recessive disease scope, cutis laxa/De Barsy framing, amino-acid depletion, hyperammonemia, cataracts, microcephaly, developmental delay, growth failure, and connective tissue involvement.
Curation actions
- Keep the generated mapping to
ALDH18A1_De_Barsy_Spectrum.yaml. - Use the ARCL3A/De Barsy branch as the primary context for this IEMbase record.
- Consider adding IEMbase's mitral valvulitis, corneal clouding, tortuous vessels, osteoporosis, hip dislocation, corpus-callosum/white-matter findings, brain creatine, and skeletal detail after source verification.