Abstract
Extract: An infant suffering from metabolic acidosis attributable to hyperlactatemia (6.1 mmol/liter) accompanied by hyperalaninemia (1 mmol/liter) and hyperserinemia (0.6 mmol/liter) is described. The urinary excretion of lactate and pyruvate was greatly elevated; the lactate to pyruvate ratio was normal. The urine showed low levels of citrate, isocitrate, and cis-aconitate, and low or normal levels of α-oxoglutarale, succinate, malate, and methylmalonate. Aspartate was slightly elevated in serum and urine, indicating a corresponding increase of its α-ketoacid oxaloacetate. These patterns of organic acids and amino acids suggested an in vivo defect in the oxidation of pyruvate. Fibroblasts cultured from skin biopsy from the patient metabolized radioactive pyruvate (final concentration 0.04–2 mmol/liter) to CO2 at rates from 5 to 17% of that of fibroblasts from normal control subjects. Enzyme studies with fibroblast sonicates revealed a severe deficiency of the pyruvate dehydrogenase complex (about 8% of normal), and this error was localized to the first unit of the complex, i.e., the pyruvate dehydrogenase (about 4% of normal). Fibroblasts from both parents metabolized pyruvate to CO2 at a slightly reduced rate, suggesting parental heterozygosity.
Speculation: An exact classification, which may have both prognostic and therapeutic implications, of patients suffering from the heterogenous group of diseases, congenital lactic acidosis, will be possible only when the various underlying defects have been demonstrated. Since we are probably dealing with errors localized close to the center of the energy metabolism, sophisticated in vivo and in vitro studies will be required to reach this goal. However, we expect each defect to give rise to secondary derangements in the patterns of organic acids and amino acids in serum and urine, which are more or less typical for each defect. Once these patterns are known, a precise biochemical diagnosis may be reached by comparatively simple examinations.
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Strömme, J., Borud, O. & Moe, P. Fatal Lactic Acidosis in a Newborn Attributable to a Congenital Defect of Pyruvate Dehydrogenase. Pediatr Res 10, 62–66 (1976). https://doi.org/10.1203/00006450-197601000-00012
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DOI: https://doi.org/10.1203/00006450-197601000-00012
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