[Chronic hyperammonemia with orotic aciduria: evidence of pyrimidine pathway stimulation (author's transl)]

We have investigated a 3 year old girl with mental and physical retardation, chronic hyperammonemia and orotic aciduria. Plsma glutamine, alanine and proline concentrations were high. Alanine was present in her urine. She excreted only half the urea of control subjects on a similar protein intake. Raising protein intake induced NH4 intoxication with convulsion. Orotic aciduria was present (max: 693 mg/day) and was related to NH4 levels. Red blood cell orotate phosphoribosyl transferase and orotidine decarboxylase activieé were normal, eliminating congenital orotic aciduria, with induction of activity seen on repeated assay during protein load (form 1.37 to 7.5 nmole/109 RBC/hr). Blood ammonia rose with ornithine load, while ornithine levels were twice that of controls. Citrulline was normally metabolized. Although lacking liver assay, we have provided evidence of partial ornithine carbamyl transferase deficiency. The importance of orotic aciduria for ammonia detoxication in partial OCT deficiency is shown, and its possible effect on liver lipoprotein synthesis discussed. Our investigation also confirmed that OCT activity is not present in normal leukocytes rendering them useless for OCT deficiency diagnosis.