Fibroblast culture GM6056 was derived from a skin biopsy of a 4-month-old Mexican-American fe male. On the first day of life, the infant developed metabolic acidosis with a blood lactate concentration of 160 mg/dl. Blood and urine organic acid profiles obtained by gas-liquid chromatography (Perry, 1970) revealed large amounts of lactate, acetoacetate, and (3-hydroxybutyrate. The clinical condition did not re spond to a diet consisting of low carbohydrate, high fat, and high protein supplemented with thiamine, biotin, lipoic acid, and pyridoxine (Hommes, 1980), and the patient failed to thrive. A diagnosis of pyruvate carboxylase deficiency, McKusick No. 26615 (McKusick, 1983), was estab lished by a specific enzyme assay (Hansen, 1979) for pyruvate carboxylase activity in fibroblasts (table I). Pyruvate oxidation studies employing intact fibro blasts and using differentially labeled 14C-pyruvate as the substrate (Blass, 1970) revealed an oxidation rate comparable to that of control fibroblasts. This ob servation ruled out a defect in the pyruvate dehy drogenase complex system. The absence of pyruvate carboxylase activity and the observed normal propionyl-CoA carboxylase activity (Wolf, 1978) in dicated an isolated defect in pyruvate carboxylase and not a multiple carboxylase deficiency. These findings are consistent with the lack of clinical improvement after prolonged biotin supplementation. The patient's clinical picture improved markedly on a diet containing large amounts of asparagine, glutamine, aspartic acid, and glutamic acid. At 9 months of age. the patient had an IQ of 66 and a DQ (developmental quotient) of 71 with markedly retard-