• Definition: a rare inherited genetic disorder that is characterized by an elevation of orotic acid in the serum and urine due to defective UMP synthase
• Inheritance: autosomal recessive
• Pathophysiology
  • UMP synthase normally converts orotic acid into uridine monophosphate.
  • Deficiency of UMP synthase → accumulation of orotic acid in serum and urine
  • Defective de novo synthesis of pyrimidine nucleotides
• Clinical features
  • Manifests in early childhood
  • Growth faltering
  • Delayed physical and mental development
  • Megaloblastic anemia, which does not respond to folate and vitamin B12 supplementation
  • Orotic acid crystalluria
• Diagnostics
  • Serum
    • ↓ Hemoglobin
    • ↑ Mean corpuscular volume
    • ↑ Orotic acid
    • Normal ammonia levels and BUN
  • Urine: ↑ orotic acid
• Treatment
  • Uridine monophosphate substitution
  • Uridine triacetate substitution