A neonate develops hyperammonemia (ammonia 800 μmol/L), lethargy, and poor feeding on day 2 of life. Plasma citrulline and urine orotic acid are both normal. Which enzyme deficiency is most likely responsible?

• A Ornithine transcarbamylase (OTC)
• B Carbamoyl phosphate synthetase I (CPS-I) ✓
• C Argininosuccinate synthetase
• D Argininosuccinate lyase

Explanation

CPS-I deficiency causes severe early hyperammonemia with normal citrulline and absent orotic acid because carbamoyl phosphate production is blocked upstream. OTC deficiency also causes low citrulline but elevated orotic acid because excess carbamoyl phosphate shunts into pyrimidine synthesis. CPS-I requires N-acetylglutamate as an allosteric activator.

Reference: Harrison's Principles of Internal Medicine, 20th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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