Strömme J H, Borud O, Moe P J
Pediatr Res. 1976 Jan;10(1):62-6. doi: 10.1203/00006450-197601000-00012.
An infant suffering from metabolic acidosis attributable to hyperlactatemai (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 alpha-oxoglutarate, succinate, malate, and methylmalonate. Aspartate was slightly elevated in serum and urine, indicating a corresponding increase if its alpha-ketoacid oxaloacetatae. 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.
本文描述了一名患有代谢性酸中毒的婴儿，其病因是高乳酸血症（6.1毫摩尔/升），同时伴有高丙氨酸血症（1毫摩尔/升）和高丝氨酸血症（0.6毫摩尔/升）。乳酸和丙酮酸的尿排泄量大幅升高；乳酸与丙酮酸的比值正常。尿液中柠檬酸、异柠檬酸和顺乌头酸水平较低，α-酮戊二酸、琥珀酸、苹果酸和甲基丙二酸水平较低或正常。血清和尿液中的天冬氨酸略有升高，表明其α-酮酸草酰乙酸相应增加。这些有机酸和氨基酸模式提示丙酮酸氧化存在体内缺陷。从患者皮肤活检培养的成纤维细胞将放射性丙酮酸（终浓度0.04 - 2毫摩尔/升）代谢为二氧化碳的速率为正常对照受试者成纤维细胞的5%至17%。对成纤维细胞超声提取物进行的酶学研究显示丙酮酸脱氢酶复合物严重缺乏（约为正常水平的8%），且该缺陷定位于复合物的第一个单元，即丙酮酸脱氢酶（约为正常水平的4%）。父母双方的成纤维细胞将丙酮酸代谢为二氧化碳的速率略有降低，提示父母为杂合子。
