The Genetic Heterogeneity of Lactic Acidosis: Occurrence of Recognizable Inborn Errors of Metabolism in a Pediatric Population with Lactic Acidosis

Abstract

Summary: A total of 40 skin fibroblast cultures from pediatric cases of lactic acidosis were subjected to a series of tests designed to elucidate the nature of an underlying defect in metabolism. Of these 40 cases, in 14 we were able to define the following problems. Pyruvate carboxylase deficiency was evident in five cases showing 14CO₂ from [3-¹⁴C]pyruvate was deficient at 13 and 28% of normal activity, respectively, which we consider to be indicative of reduced activity of the Krebs' cycle. The grounds for the diagnosis of these 14 affected cases are documented, and the clinical presentation of these enzyme deficiencies is assessed in the light of present knowledge about lactic acidosis. Speculation: We speculate that the continuing use of the comprehensive diagnostic approach to pediatric cases of lacticacidosis as set out in this manuscript will eventually reveal the incidence, character, and clinical manifestations peculiar to the various enzyme deficiencies which collectively contribute to this syndrome.