Propionyl-CoA carboxylase deficiency in a patient with biotin-responsive 3-methylcrotonylglycinuria

The abnormal metabolites 3-hydroxypropionic acid (1.6-4.0 mg/day) and methylcitric acid (3.7-5.8 mg/day) were identified and quantitated in the urine of a patient in whom biotin-responsive 3-methylcrotonylglycinuria and deficiency of 3-methylcrotonyl-CoA carboxylase had previously been documented. The level of excretion of these metabolites was in the lower range of those found in patients with propionic acidemia in whom there is a deficiency of propionyl-CoA carboxylase. The activity of this enzyme in fibroblasts derived from the patient and grown in media low in biotin was 4% of normal. This is the range of patients with propionyl-CoA carboxylase deficiency. Documented deficiency in this patient of two carboxylase, both of which contain biotin, suggests that the primary defect is in the metabolism of biotin.