E1 PYRUVATE-DEHYDROGENASE DEFICIENCY IN A CHILD WITH MOTOR NEUROPATHY
E1 PYRUVATE-DEHYDROGENASE DEFICIENCY IN A CHILD WITH MOTOR NEUROPATHY
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DOI：
10.1203/00006450-199303000-00016
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发表时间：
1993-03-01
影响因子：
3.6
通讯作者：
MARSAC, C
中科院分区：
文献类型：
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作者：
BONNE, G;BENELLI, C;MARSAC, C
我们报告了一个男孩的病例，他在18个月和3岁的时候，在感染发作期间发生了运动神经病变。当他7岁时，他出现持续性虚弱和反射不全；他的静息乳酸和丙酮酸值分别为3.65 mm和398 um(对照组：1.1+/-0.3 mm和90+/-22 um)，运动试验显示乳酸酸中毒(13.6 mm；对照组：6.4+/-1.3 mm)，丙酮酸水平高(537 um；对照组：176+/-15 um)和低乳酸/丙酮酸比值(24.2；对照组：35+/-2)。对肌肉线粒体的极谱研究结果表明，丙酮酸氧化存在缺陷(丙酮酸17 ng原子O/min/mg蛋白质；对照组：115+/-42)，而谷氨酸、棕榈酰肉碱和琥珀酸是良好的呼吸底物。肌肉线粒体和新鲜单个核细胞中的总丙酮酸脱氢酶复合体活性显著降低(分别为9.7nmol(CO_2)-C~(-14)/分钟/mg蛋白；对照组：123nmol(CO_2)-C~(-14)/分钟/mg蛋白；0.733+/-0.03)。在肌肉线粒体中的免疫化学分析表明，缺乏α和βE1PDHC亚单位。经500 mg/d硫胺素治疗2年后，患者临床症状改善。对编码PDHC E1Alpha亚单位的X染色体主要突变区域(外显子10和11)的遗传学研究没有发现任何突变。这些数据表明，尽管遗传上不同，但该病例进入了一种非常罕见的无脑功能障碍的PDHC缺乏症患者类别，并通过硫胺素+L-卡尼汀治疗得到改善。
We report the case of a boy who developed a motor neuropathy during infectious episodes at 18 mo and 3 y of age. When he was 7 y old, he suffered persistent weakness and areflexia; his resting lactate and pyruvate values were 3.65 mM and 398 muM, respectively (controls: 1.1 +/- 0.3 mM and 90 +/- 22 muM), and an exercise test demonstrated a lactic acidosis (13.6 mM; controls: 6.4 +/- 1.3 mM) with a high pyruvate level (537 muM; controls: 176 +/- 15 muM) and a low lactate/pyruvate ratio (24.2; controls: 35 +/- 2). The results of polarographic studies on muscle mitochondria suggested a defect in pyruvate oxidation (pyruvate 17 ng atom O/min/mg protein; controls: 115 +/- 42), whereas glutamate, palmitoylcarnitine, and succinate were good respiratory substrates. The activity of total pyruvate dehydrogenase complex (PDHC) in muscle mitochondria and in fresh mononuclear cells was markedly decreased (9.7 and 0.054 nmol (CO2)-C-14/min/mg protein, respectively; controls: 123 +/- 4.5 and 0.733 +/- 0.03, respectively). Immunochemical analysis in muscle mitochondria demonstrated an absence of the alpha and beta E1 PDHC subunits. After 2 y of treatment with 500 mg/d thiamine, the patient was clinically improved. A genetic study of the main regions of mutations (exon 10 and 11) in the X chromosome encoding for the E1alpha subunit of PDHC did not show any mutation. These data indicate that, although genetically different, this case enters in a very rare category of patients with PDHC deficiency without cerebral dysfunction and improved by thiamine + L-carnitine therapy.