A new inborn error of metabolism, characterized by urinary excretion of substantial amounts of β-hydroxyisovaleric acid and β-methylcrotonylglycine, is described. The disorder is most likely due to a defect in the biotin-dependent enzyme β-methylcrotonyl-CoA carboxylase in the leucine degradation pathway. The patient, a 4½-month-old girl, suffered from neurological symptoms similar to those of Werdnig-Hoffmann's disease. No episodes of acidosis could be detected. In periods the urine had a peculiar odor, like that of cat's urine. Relatively large doses of biotin (0.25 mg/day) did not influence the condition. On a diet containing the minimum requirement of leucine, the daily excretion of β-hydroxyisovaleric acid dropped from 400 mg to about 50 mg and β-methylcrotonylglycine from 100 mg to 50 mg. However, the clinical course was unaltered and the patient died at 9 months of age from bronchopneumonia. Biochemically, as well as clinically, the findings are distinctly different from previously described errors in the leucine metabolism.
An Inborn Error of Metabolism with the Urinary Excretion of -Hydroxy-Butyric Acid and Phenylpyruvic Acid