A 3-day-old neonate has lethargy, vomiting, respiratory alkalosis, and a plasma ammonia level of 480 micromol/L. Urine orotic acid is markedly elevated. Which enzyme deficiency explains this combination?

• A Carbamoyl phosphate synthetase I
• B UMPS bifunctional enzyme (orotate phosphoribosyltransferase and OMP decarboxylase)
• C Ornithine transcarbamoylase ✓
• D N-acetylglutamate synthetase

Explanation

In ornithine transcarbamoylase deficiency, mitochondrial carbamoyl phosphate cannot enter the urea cycle and leaks into the cytosol, where it feeds pyrimidine synthesis and produces orotic aciduria together with hyperammonemia. Hereditary orotic aciduria due to UMPS deficiency also raises orotate but never causes hyperammonemia, because the urea cycle is intact.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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