A newborn male is detected on neonatal screening with elevated plasma citrulline (1200 micromol/L; normal <40) and ammonia (350 micromol/L). Argininosuccinate is absent in urine. Urine orotic acid is markedly elevated. Which enzyme defect is MOST consistent with this pattern?
- A Ornithine transcarbamylase (OTC) deficiency
- B Argininosuccinate synthetase deficiency (Citrullinemia type I) ✓
- C Argininosuccinate lyase deficiency
- D Carbamoyl phosphate synthetase I (CPS-I) deficiency
Explanation
Markedly elevated plasma citrulline (>1000 micromol/L, termed 'hypercitrullinemia') with elevated ammonia and absent argininosuccinate in urine points to argininosuccinate synthetase deficiency (Citrullinemia type I). Citrulline accumulates because it cannot condense with aspartate to form argininosuccinate. Elevated orotic acid occurs because excess carbamoyl phosphate (which cannot be used in the urea cycle) is diverted to pyrimidine synthesis. OTC deficiency also shows elevated orotic acid but citrulline is low/normal because citrulline synthesis is impaired. CPS-I deficiency shows low citrulline and low/absent orotic acid (no carbamoyl phosphate made). Argininosuccinate lyase deficiency causes argininosuccinic aciduria (elevated argininosuccinate in urine).
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.