A 3-year-old child presents with progressive intellectual disability, seizures, and intermittent episodes of encephalopathy triggered by high-protein meals. Plasma amino acids show elevated citrulline and ammonia; urinary orotic acid is ELEVATED. Which urea cycle enzyme is deficient?

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

Explanation

OTC deficiency is the most common urea cycle disorder and is X-linked. Carbamoyl phosphate accumulates and overflows into the cytosol where it enters the pyrimidine synthesis pathway, producing excess orotic acid — the key distinguishing feature from CPS-I deficiency (which also causes hyperammonemia but does NOT elevate orotic acid). Citrullinemia type I causes elevated citrulline. OTC deficiency gives elevated citrulline (mild) plus markedly elevated orotic acid.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.