Orotic aciduria

• Pathophysiology
  • Inheritance: AR.
  • Defect: UMP synthase deficiency (Pyrimidine synthesis pathway).
  • Result: Inability to convert orotic acid → UMP.
• Clinical Features
  • Failure to thrive, developmental delay.
  • Megaloblastic anemia that is refractory to B12/Folate.
  • NO hyperammonemia.
• Labs & Diff Dx
  • Urine: ↑ Orotic acid.
  • Key Distinction: t
    • Orotic Aciduria: ↑ Orotic acid + Normal Ammonia.
    • OTC Deficiency: ↑ Orotic acid + ↑ Ammonia (Urea cycle defect).
• Treatment
  • Uridine administration (bypasses enzyme block).