Isolated biotin-resistant deficiency of 3-methylcrotonyl-CoA carboxylase presenting as a clinically severe form in a newborn with fatal outcome.

The son of Kurdish, consanguineous parents (cousin marriage) presented from the first day of life with initially focal and later generalized attacks of epileptic seizures and a severe generalized muscular hypotonia. Urinary excretion of 3-hydroxyisovalerate and of 3-methylcrotonylglycine was persistently increased. Diagnosis of isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency was confirmed in cultured fibroblasts. Psychomotor retardation was progressive, seizures and marked EEG abnormalities persisted. Treatment with leucine and protein-resistricted diet under hospital control did not significantly improve these conditions. The patient died from a cardiac and circulatory failure after a prolonged epileptic attack, with bronchial aspiration. The non-responsiveness of our patient to therapy and the fatal outcome indicate the existence of a severe neonatal variant of this otherwise rather benign genetic enzyme deficiency.