Diagnosis of ornithine carbamoyl transferase deficiency and heterozygote detection with allopurinol loading test

BACKGROUND: Allopurinol loading test is based on the inhibition of pyrimidine biosynthesis and the subsequent increase in orotic acid excretion caused by a single dose of allopurinol. Abnormally elevated amounts of orotic acid excretion are demonstrated in ornithine carbamoyl transferase (OCT) deficiency patients and heterozygotes as well as in other disorders of urea cycle. Biochemical studies performed for the diagnosis of one patient and carrier detection in her family are presented. METHODS: Amino acids: ion exchange chromatography; ammonium: method of Van Anken and Shiphorst; orotic acid: modification of Adachi et al, and allopurinol test following Brusilow et al. RESULTS: The characteristic amino acid profile of the patient together with her clinical history suggested the diagnosis of OCT deficiency, which was confirmed with protein and allopurinol loading test. The heterozygote condition became evident only by means of allopurinol test in 2/5 female relatives. CONCLUSIONS: Allopurinol test is a useful tool for the preliminary investigation of urea cycle function, avoiding the possible hyperammonemia caused by other test, and permitting extensive familial studies without hospitalization. It results more informative than the protein loading test.