Orotic aciduria (type I hereditary) is characterised by megaloblastic anaemia, failure to thrive, and massive urinary orotic acid excretion. It is caused by deficiency of which bifunctional enzyme?
- A Carbamoyl phosphate synthetase I (CPS-I)
- B Dihydroorotate dehydrogenase (DHODH)
- C UMP synthase (containing both orotate phosphoribosyltransferase and OMP decarboxylase activities) ✓
- D CAD trifunctional enzyme (CPS-II/ATCase/DHOase)
Explanation
Hereditary orotic aciduria type I is caused by deficiency of UMP synthase, a bifunctional enzyme containing both orotate phosphoribosyltransferase (OPRT) and OMP decarboxylase (OMPDC) activities on a single polypeptide. OPRT converts orotic acid + PRPP to OMP; OMPDC then decarboxylates OMP to UMP. Deficiency of UMP synthase causes orotic acid to accumulate and spill into urine. Treatment with uridine bypasses the block. CPS-I deficiency causes hyperammonaemia (urea cycle). DHODH is in the de novo pathway earlier and is targeted by leflunomide. CAD deficiency would block the entire de novo pyrimidine pathway upstream.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.