Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase.- Autosomal recessive.

Presents in children as failure to thrive, developmental delay, and megaloblastic anemia refractory to folate and B₁₂.

Findings:- Orotic acid in urine- No hyperammonemia (vs ornithine transcarbamylase deficiency – ↑ orotic acid with hyperammonemia).

Treatment: uridine monophosphate or uridine triacetate to bypass mutated enzyme