Orotic aciduria without hyperammonaemia is characteristic of deficiency of which enzyme?

• A OTC (ornithine transcarbamylase)
• B Carbamoyl phosphate synthetase I
• C Argininosuccinate lyase
• D UMP synthase (bifunctional enzyme with orotate phosphoribosyltransferase and OMP decarboxylase) ✓

Explanation

UMP synthase deficiency (hereditary orotic aciduria type I) blocks pyrimidine de novo synthesis downstream of carbamoyl phosphate, causing orotic acid accumulation with megaloblastic anaemia but NO hyperammonaemia because the urea cycle is intact. OTC deficiency also causes orotic aciduria but with severe hyperammonaemia (carbamoyl phosphate overflows into cytosol). CPS-I and argininosuccinate lyase deficiency cause hyperammonaemia without orotic aciduria.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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