Hereditary orotic aciduria: results of a screening survey

Urine from 1,358 mentally retarded subjects was screened for the presence of elevated concentrations of orotic acid and orotidine. This survey was conducted in search of occult variants of hereditary orotic aciduria which might be associated with mental retardation. Although no homozygous variants were detected, 9 subjects with persistently abnormal urinary screening tests were discovered. Assays of erythrocyte orotidylate decarboxylase and phosphoribosyltransferase enzymes showed deficient activities for 2 of these subjects typically found in red cells of persons heterozygous for hereditary orotic aciduria. The same studies were conducted on urine and blood samples from the families of the affected subjects, and additional family members were also found to be affected. Detection of two unrelated heterozygotes among so small a screened population suggests, as previously noted, a higher frequency of the abnormal gene than that indicated by the extreme rarity of the homozygous condition. This study demonstrates the usefulness of the urinary screening test mass surveys and indicates the need for further study of the prevalence of the mutant gene.