Hereditary orotic aciduria (type I) is caused by deficiency of UMP synthase, a bifunctional enzyme. Which of the following does NOT occur in this condition?
- A Megaloblastic anemia that does not respond to vitamin B12 or folate
- B Orotic acid crystalluria
- C Hyperammonemia responding to arginine supplementation ✓
- D Retardation of growth and development
Explanation
Hereditary orotic aciduria is characterized by: orotic acid accumulation and crystalluria, megaloblastic anemia unresponsive to B12/folate (due to pyrimidine deficiency impairing DNA synthesis), and failure to thrive. Hyperammonemia responding to arginine is characteristic of urea cycle defects (specifically ornithine transcarbamylase/OTC deficiency), where excess carbamoyl phosphate overflows into the pyrimidine synthesis pathway, causing secondary orotic aciduria — but this is distinguishable by the presence of hyperammonemia. In primary hereditary orotic aciduria, ammonia is normal because the urea cycle is intact. Treatment is with uridine supplementation.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.