Congenital Orotic Aciduria: Demonstration of an Enzyme Defect in Leukocytes and Comparison with Drug-induced Orotic Aciduria

1. Leukocytes from presumed heterozygotes of congenital orotic aciduria have been found to exhibit a partial defect in the metabolism of orotic acid. In disrupted cell preparations, orotidylic decarboxylase activity was reduced. Assay of orotidylic pyrophosphorylase activity proved to be unsatisfactory in leukocyte preparations.

2. Orotic aciduria and orotidinuria were produced by the administration of 6-azauridine to patients with chronic myelocytic leukemia. This drug-induced impairment of pyrimidine nucleotide biosynthesis has been compared to the genetically determined disorder.

3. A summary of enzymatic defects previously demonstrated in hemic cells in human genetic disorders has been presented.