A neonate develops hyperammonemia, encephalopathy, and respiratory alkalosis within 48 hours of birth. Plasma amino acids show marked elevation of citrulline with very low argininosuccinate. Orotic acid in urine is elevated. What enzyme is deficient?

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

Explanation

Citrullinemia type I results from argininosuccinate synthetase deficiency. Citrulline accumulates because it cannot condense with aspartate to form argininosuccinate. Elevated citrulline with absent or very low argininosuccinate distinguishes this from other urea cycle defects. Orotic acid is elevated because excess carbamoyl phosphate spills into the pyrimidine synthesis pathway. OTC deficiency also elevates orotic acid but causes very low citrulline (not high). CPS-I deficiency causes low citrulline with no orotic aciduria. This distinction is essential for diagnosis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.