OROTIC ACIDURIA ASSOCIATED WITH THE FORM- IMINOTRANSFERASE/CYCLODEAMINASE DEFICIENCY: 189

A 12 year-old girl with a long history of megaloblastic anemia, hypotonia and mental retardation was found to have a mild elevation of homocystine, orotic acid and orotidine and a marked increase in formiminoglutamic acid (FIGLU) in urine and plasma. Serum concentration of folate and vitamin B-12 was normal, and the activity of orotate phospho-ribosyltransferase, thymidylate synthetase, methylene tetrahydrofolate reductase and methionine synthetase in fibroblasts was in the normal range. Upon histidine loading the urinary excretion of FIGLU was app. 100 above the normal range and decreased sharply by leucovorin administration. The result of assay of fromiminotransferase/cyclodeaminase showed a 30-50 % of normal range (70-150 nmol/min/g Hb, n=15), which is comparable with the cases of the deficiency described by Arakawa's group. An interesting observation, however, is the increased level of orotic acid in this patient. Although mild the consistently elevated urinary ortate, possibly due to an increased synthesis rather than a metabolic block leads us to a speculation that the highly reactive formimino group may be a precursor of orotic acid.