title: Isolated biotin-resistant deficiency of 3-methylcrotonyl-CoA carboxylase presenting as a clinically severe form in a newborn with fatal outcome.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Berne Inselspital, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Bannwart
authors.forename: B
authors.initials: B
authors.lastname: Wermuth
authors.forename: R
authors.initials: R
authors.lastname: Baumgartner
authors.forename: T
authors.initials: T
authors.lastname: Suormala
authors.forename: U N
authors.initials: UN
authors.lastname: Weismann
mesh_terms: D000650:Amnion / Q000201:enzymology; D001710:Biotin / Q000494:pharmacology*; D019735:Carbon-Carbon Ligases; D002262:Carboxy-Lyases / Q000378:metabolism; D004035:Diet Therapy; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D008025:Ligases / Q000172:deficiency* / Q000378:metabolism; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase; D008928:Mitochondria / Q000201:enzymology; D009123:Muscle Hypotonia / Q000209:etiology; D011766:Pyruvate Carboxylase / Q000378:metabolism; D012640:Seizures / Q000209:etiology
chemical_list: D001710:Biotin; D002262:Carboxy-Lyases; D008025:Ligases; D019735:Carbon-Carbon Ligases; D011766:Pyruvate Carboxylase; C021573:methylcrotonoyl-CoA carboxylase; D043586:Methylmalonyl-CoA Decarboxylase