Hereditary Orotic Aciduria

Abstract

A new case of hereditary orotic aciduria is reported. Clinical manifestations included growth retardation, orotic acid crystalluria, and a megaloblastic anemia. Uridine therapy produced a prompt hematologic response and a rapid acceleration of growth. Orotic acid excretion on treatment ranged from 0.96 gm to 3.89 gm orotic acid per gram creatinine, and no decrease in excretion was observed when the uridine dosage was increased from 0.75 to 2.0 gm per day. Studies of the patient's erythrocytes revealed a virtual absence of the activity of orotidylic pyrophosphorylase and orotidylic decarboxylase. Previously undescribed studies of liver revealed the enzymatic deficiency in this tissue as well. Four generations of the patient's family were evaluated with erythrocyte enzyme assays and with a urinary screening test developed during the course of these studies. A subject apparently unrelated to the propositus was unexpectedly found to be a carrier of the disorder. Investigation of his family revealed other heterozygous individuals. With the pedigrees of these families, an autosomal, recessive mode of inheritance was demonstrated.