ABSTRACT
Megaloblastic anemia, failure to thrive, susceptibility to infection, crystalluria, orotic aciduria, and deficient activity of orotidylic pyrophosphorylase and orotidylic decarboxylase. Orotic aciduria represents pyrimidine nucleotide starvation in man. Administration of uridylic and cytidylic acids led to reduction in orotic acid excretion. 6-Azauridine and 6-azauracil, used in cancer chemotherapy, must be converted to their nucleotides for them to have antitumor activity; consistent with the lack of effect of uracil in orotic aciduria, 6-azauridine is 20 times more effective as an antitumor agent than azauracil. An intravenous pyelogram revealed a nephrogram effect with radiopaque material remaining in the kidney 1.5 hours after injection, presumably because of obstruction of the renal collecting tubules by crystalline orotic acid. Orotic aciduria was first reported by Huguley et al. in 1959 in a single patient who illustrated clearly the features of the disease, particularly megaloblastic anemia.
