SummaryThe 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 in the range of patients with propionyl-CoA carboxylase deficiency. Documented deficiency in this patient of two carboxylases, both of which contain biotin, suggests that the primary defect is in the metabolism of biotin.SpeculationThe deficiency of two mitochondrial carboxylases in a patient suggests the presence of a fundamental defect in either the transport of biotin or in the holocarboxylase synthetase that attaches biotin covalently to both carboxylases.