Multiple carboxylase deficiency: clinical and biochemical improvement following neonatal biotin treatment

Multiple carboxylase deficiency is characterized by deficient activities of three biotin-dependent enzymes, propionyl coenzyme A carboxylase, pyruvate carboxylase, and beta-methylcrotonyl coenzyme A carboxylase. A newborn infant was seen with metabolic ketoacidosis, hyperammonemia, organic aciduria,...

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Bibliographic Details
Published in:Pediatrics (Evanston) 1981-07, Vol.68 (1), p.113-118
Main Authors: Wolf, B, Hsia, Y E, Sweetman, L, Feldman, G, Boychuk, R B, Bart, R D, Crowell, D H, Di Mauro, R M, Nyhan, W L
Format: Article
Language:English
Subjects:
Biotin - therapeutic use
Carbon-Carbon Ligases
Carboxy-Lyases - deficiency
Electroencephalography
Humans
Infant, Newborn
Ligases - deficiency
Male
Methylmalonyl-CoA Decarboxylase
Propionates - deficiency
Pyruvate Carboxylase Deficiency Disease
Tomography, X-Ray Computed
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Summary:Multiple carboxylase deficiency is characterized by deficient activities of three biotin-dependent enzymes, propionyl coenzyme A carboxylase, pyruvate carboxylase, and beta-methylcrotonyl coenzyme A carboxylase. A newborn infant was seen with metabolic ketoacidosis, hyperammonemia, organic aciduria, seizures, and coma. Multiple carboxylase deficiency was subsequently confirmed by enzyme activity determinations in his peripheral blood leukocytes and cultured skin fibroblasts. The infant's neurologic and metabolic status improved markedly within a few days of administration of pharmacologic doses of oral biotin. His EEG, which was distinctly abnormal, became normal; his extensive computed tomography scan changes resolved, with the exception of ventricular dilation, over the next two months. After two weeks of biotin treatment the excretion of abnormal organic acid metabolites was reduced and his carboxylase activities increased to the normal range. However, the activities of these enzymes increased only to 30% to 55% of normal in fibroblasts incubated in supplemental biotin. This partial correction of enzyme activity differs from that observed in other individuals with multiple carboxylase deficiency and suggests biochemical heterogeneity in this disorder. Prompt diagnosis and intervention can avert some of the pathologic complications of this biotin-responsive condition.
ISSN:0031-4005
1098-4275
DOI:10.1542/peds.68.1.113