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PEDIATRICS Vol. 50 No. 5 November 1972, pp. 702-711
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THIAMINE-RESPONSIVE LACTIC ACIDOSIS IN A PATIENT WITH DEFICIENT LOW-KM PYRUVATE CARBOXYLASE ACTIVITY IN LIVER

Michèle G. Brunette M.D.1, Edgard Delvin Ph.D.1, Bernard Hazel F.R.C.P.1, , Charles R. Scriver M.D.1

1 Department of Pediatrics, University of Montreal and Maisonneuve Hospital, and the deBelle Laboratory for Biochemical Genetics, McGill University, and Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada

The cause of severe intermittent lactic acidosis was investigated in a female infant with profound psychomotor retardation. Hypoglycemia, hyperpyruvic acidemia, and hyperalaninemia were identified in the newborn period. A triad of lactate, pyruvate, and alanine accumulation persisted throughout infancy, and ACTH, anorexia, and high carbohydrate feeding further provoked their accumulation. Careful dietary control or thiamine-HCl supplementation (5 to 20 mg/day) ameliorated the metabolic abnormality.

Pyruvate dehydrogenase activity (which is thiamine-dependent) was normal in leukocytes and cultured skin fibroblasts. Hepatic pyruvate carboxylase activity (which is biotin-dependent) was found to comprise more than one component. There was a partial deficiency of total hepatic pyruvate carboxylase activity in the patient. The loss of activity was confined to the low-Km component of the enzyme which serves pvruvate metabolism in the physiological range.

A defect in glucogenesis causing hypoglycemia, pyruvate accumulation with lactic acidosis, and aberrant amino acid metabolism can be attributed to the abnormality of pyruvate carboxylase. The response to thiamine in our patients may reflect activation of a normal "shunt" mechanism for pyruvate disposal via pyruvate dehydrogenase.

Submitted on May 3, 1972
Accepted on June 6, 1972


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