A 10-day-old neonate is brought with lethargy, poor feeding, and vomiting after protein feeds. Plasma amino acid profile shows marked elevation of citrulline with low argininosuccinate. Urinary orotic acid is elevated. The enzyme deficiency most consistent with this presentation is:

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

Explanation

Argininosuccinate synthetase (ASS) catalyzes the condensation of citrulline with aspartate to form argininosuccinate; its deficiency (citrullinemia type I) causes citrulline accumulation. The elevated orotic acid results from carbamoyl phosphate overflowing from the mitochondria into the cytoplasm, entering the pyrimidine synthesis pathway and eventually producing orotic acid. Low argininosuccinate is expected because the reaction forming it is blocked. OTC deficiency would show low citrulline (not high), while CPS-I deficiency would show low citrulline without elevated orotic acid.

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

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Written and medically reviewed by the StethoPrep medical team.