IEMbase 0012: NAGS-related N-acetylglutamate synthase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 12 |
| Nosology | 1.1.01.01 |
| Gene | NAGS |
| External IDs | OMIM:237310 |
| Generated mapping | AMBIGUOUS by alias_exact:n acetylglutamate synthase deficiency |
| Candidate DisMech targets | N-Acetylglutamate_Synthase_Deficiency.yaml; Urea_Cycle_Disorder.yaml#N-Acetylglutamate Synthase Deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
Characteristic clinical features are coma, developmental delay, encephalopathy, and vomiting, again with stronger neonatal/infantile acute-decompensation signal. Additional features include failure to thrive, feeding difficulty/protein aversion, seizures, and neonatal temperature instability.
The biochemical profile includes high ammonia, increased plasma and CSF glutamine, low arginine, very low citrulline, normal argininosuccinic acid, and low/normal urinary orotic 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 covers hyperammonemia, encephalopathy, vomiting, lethargy, seizures, intellectual disability, failure to thrive, headache, cerebral edema, coma, and respiratory alkalosis. Biochemical entries cover plasma ammonia, plasma glutamine, plasma citrulline, urine orotic acid, and N-acetylglutamate. Treatments include carglumic acid, dietary protein management, nitrogen scavengers, extracorporeal ammonia removal, acute-crisis supportive care, citrulline/arginine, genetic counseling, and a carbamylglutamate therapeutic trial.
The Urea Cycle Disorder umbrella subtype causes the exact-alias ambiguity.
Concordance and completeness
Judgement: phenotype concordance is high, but mapping should prefer the standalone disease over the umbrella subtype for disease-level crosswalks.
IEMbase adds feeding difficulty/protein aversion and neonatal temperature instability. DisMech adds headache, cerebral edema, respiratory alkalosis, NAG biochemistry, and explicit carglumic-acid therapeutic testing.
Curation actions
- Resolve crosswalk ambiguity by treating
N-Acetylglutamate_Synthase_Deficiency.yamlas the canonical target. - Consider adding feeding difficulty/protein aversion if supported by evidence.
- Consider whether peritoneal dialysis needs explicit mention or is adequately covered by extracorporeal ammonia removal.