A neonate develops severe hyperammonemia (ammonia 900 µmol/L) within 24 hours of birth with respiratory alkalosis. Plasma citrulline is undetectable, and urine orotic acid is low. Which enzyme deficiency is most likely?
- A Carbamoyl phosphate synthetase I ✓
- B Argininosuccinate synthetase
- C Ornithine transcarbamylase
- D Argininosuccinate lyase
Correct answer: A. Carbamoyl phosphate synthetase I
Explanation
CPS-I deficiency causes early hyperammonemia with low citrulline and low orotic acid because carbamoyl phosphate is not produced, so no substrate flows to pyrimidine synthesis. OTC deficiency also shows low citrulline but elevated orotic acid because excess carbamoyl phosphate shunts into pyrimidine synthesis. This distinction is repeatedly tested.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.