IEMbase 0011: CPS1-related carbamoyl phosphate synthetase I deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 11 |
| Nosology | 1.1.02.01 |
| Gene | CPS1 |
| External IDs | OMIM:237300 |
| Generated mapping | AMBIGUOUS by alias_exact:carbamoyl phosphate synthetase i deficiency |
| Candidate DisMech targets | Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml; Urea_Cycle_Disorder.yaml#Carbamoyl Phosphate Synthetase I Deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
Characteristic clinical features are coma, developmental delay, encephalopathy, and vomiting, with stronger neonatal/infantile intensity for acute decompensation. Additional features include failure to thrive, feeding difficulty/protein aversion, seizures, and neonatal temperature instability.
The biochemical profile is urea-cycle proximal: increased ammonia, increased glutamine, low arginine, very low citrulline, normal argininosuccinic acid, and low/normal urinary orotic acid. IEMbase also lists mild/variable urinary 3-methylglutaconic acid.
Treatments include protein-defined diet, arginine or citrulline, nitrogen-scavenger drugs, carglumic acid, hemodialysis, peritoneal dialysis, and liver transplantation.
DisMech phenotype coverage
The standalone DisMech disease is the best curation target. It captures hyperammonemia, episodic ammonia intoxication, respiratory insufficiency, aminoaciduria, hypoargininemia, encephalopathy, seizures, coma, developmental delay, intellectual disability, hypotonia, vomiting, lethargy, microcephaly, cerebral edema, abnormal white matter, and atypical behavior. Biochemical entries cover plasma ammonia, citrulline, glutamine, urinary orotic acid, and alanine. Treatments cover diet, nitrogen scavengers, citrulline/arginine, carglumic acid, dialysis, liver transplantation, and genetic counseling.
The Urea Cycle Disorder umbrella also includes a subtype with the same name,
which explains the generated ambiguous match.
Concordance and completeness
Judgement: phenotype concordance is high, but mapping should prefer the standalone disease over the umbrella subtype for one-to-one IEMbase crosswalks.
IEMbase adds feeding difficulty/protein aversion and neonatal temperature instability, which are not explicit in the standalone DisMech entry. DisMech adds respiratory insufficiency, hypotonia, lethargy, microcephaly, cerebral edema, white matter abnormalities, and broader neurologic sequelae.
Curation actions
- Resolve crosswalk ambiguity by treating
Carbamoyl_Phosphate_Synthetase_I_Deficiency.yamlas the canonical target. - Consider whether umbrella subtype aliases should be de-prioritized in generated exact-alias mapping.
- Consider adding feeding difficulty/protein aversion if supported by evidence.