Pyruvate therapy for Leigh syndrome due to cytochrome c oxidase deficiency
Pyruvate therapy for Leigh syndrome due to cytochrome c oxidase deficiency
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DOI：
10.1016/j.bbagen.2009.07.008
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发表时间：
2010-03-01
影响因子：
3
通讯作者：
Tanaka, Masashi
中科院分区：
文献类型：
--
作者：
Komaki, Hirofumi;Nishigaki, Yutaka;Tanaka, Masashi
背景：最近，我们提出了丙酮酸治疗线粒体疾病的治疗潜力。Leigh综合征是一种进行性神经退行性疾病，归因于无论是线粒体或核DNA突变。方法：在试图规避线粒体功能障碍，我们口服丙酮酸钠，并分析其对一个11岁的女性Leigh综合征由于细胞色素c氧化酶缺乏症伴心肌病的影响。结果：患者运动不耐症明显改善，能正常跑步。超声心动图显示左心室射血分数和缩短分数均有所改善。心电图显示倒置T波改善。当由于胃肠道感染而中断丙酮酸盐给药时，血清乳酸水平升高，血清丙酮酸水平降低，表明丙酮酸盐给药可有效降低乳酸盐/丙酮酸盐比值。结论：这些数据表明，丙酮酸盐治疗至少在细胞色素c氧化酶缺乏症患者中可有效改善运动不耐受。丙酮酸钠的管理可能证明有效的其他患者与细胞色素c氧化酶缺乏症由于线粒体或核DNA突变。(C)2009 Elsevier B. V.保留所有权利。
Background: Recently we proposed the therapeutic potential of pyruvate therapy for mitochondrial diseases. Leigh syndrome is a progressive neurodegenerative disorder ascribed to either mitochondrial or nuclear DNA mutations.Methods: In an attempt to circumvent the mitochondrial dysfunction, we orally applied sodium pyruvate and analyzed its effect on an 11-year-old female with Leigh syndrome due to cytochrome c oxidase deficiency accompanied by cardiomyopathy. The patient was administered sodium pyruvate at a maintenance dose of 0.5 g/kg/day and followed up for 1 year.Results: The exercise intolerance was remarkably improved so that she became capable of running. Echocardiography indicated improvements both in the left ventricle ejection fraction and in the fractional shortening. Electrocardiography demonstrated amelioration of the inverted T waves. When the pyruvate administration was interrupted because of a gastrointestinal infection, the serum lactate level became elevated and the serum pyruvate level, decreased, suggesting that the pyruvate administration was effective in decreasing the lactate-to-pyruvate ratio.Conclusions: These data indicate that pyruvate therapy was effective in improving exercise intolerance at least in a patient with cytochrome c oxidase deficiency.General significance: Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations. (C) 2009 Elsevier B.V. All rights reserved.