Table.
Urea cycle defects
| Enzyme deficiency | Location | Incidence | Genetics | Presentation | Distinct labs |
|---|---|---|---|---|---|
| 1. CPS1: Carbamoyl phosphate synthetase | Mitochondria | 1:1,300,000 | AR | ↑↑NH3 in newborns | +NH3, low CIT, low ARG, normal urine OA |
| 2. OTC: Ornithine transcarbamylase | Mitochondria | 1:56,500 0–30% EA | X-linked dominant | Risk of ↑NH3 high in pregnancy | +OR, +UR, +UOA, low plasma CIT |
| 3. ASS: Argininosuccinic acid synthetase (citrullinemia) | Cytosol | 1:250,000 | AR | Some nitrogen incorp in UC | ++CIT, absent AS, fibroblast EA |
| 4. ASL: Argininosuccinate lyase (argininosuccinic aciduria) | Cytosol | 1:218,750 | AR | Rap in infants, Rx ARG | +CIT, +ASA |
| 5. ARG: Arginase (hyperargininemia) | Cytosol | 1:950,000 | AR | Often normal NH3, spasticity, ataxia | +ARG |
| 7. NAGS: N-acetylglutamate synthetase | Mitochondria | 1:2,000,000 | AR | ↑NH3 may respond to NAG | +NH3 |
| 8. ORNT1: Ornithine transporter | Gene mutation | Membrane transporter | +NH3,+OR, +homocitrulline |
AR indicates autosomal recessive; ARG, arginine; AS, argininosuccinate; ASA, argininosuccinate acid; CIT, citrulline; EA, enzyme assay; NAG, N-acetylglutamate; NH3, ammonia; OA, orotic acid; OR, ornithine; UC, urea cycle; UOA, urine orotic acid; UR, uracil.