Study of mitochondorial disease with Leigh syndrome and the therapy

我们分析了60例日本Leigh综合征患者培养的淋巴母细胞的生化和分子缺陷。在30例患者（50%）中确定了缺陷，15例患者存在酶缺陷; 5例患者存在丙酮酸脱氢酶复合物（PDHC），4例患者存在呼吸链复合物I，6例患者存在细胞色素c氧化酶（考克斯）。15例患者存在线粒体DNA点突变（A8344 G 1例，T8993 C 2例，T8993 G 12例），表明培养的淋巴母细胞对阐明Leigh综合征的病因是有用的，并且日本Leigh综合征患者中mtDNA突变发生率更高。12例T8993 G突变的患者中有5例与West综合征相关，只有该突变的患者患有West综合征。这些发现表明，与Leigh综合征相关的West综合征患者由于T8993 G突变而存在缺陷的可能性很高。4名PDHC缺乏症患者表现出对硫胺素焦磷酸盐的亲和力降低，硫胺素治疗导致临床改善，表明这4名患者具有硫胺素反应性PDHC缺乏症，高剂量的硫胺素可能在由于这种类型的PDHC缺乏症导致的Leigh综合征患者神经异常的早期阶段有用

We analyzed the biochemical and molecular defects in cultured lymphoblastoid cells that were obtained from 60 Japanese patients with Leigh syndrome. Defects were determined in 30 patients (50%), and 15 patients had enzyme defects ; 5 patients had pyruvate dehydrogenase complex (PDHC), 4 patients had respiratory chain complex I, and 6 patients had cytochrome c oxidase (COX). A point mutation of mitochondrial DNA (mtDNA) was found in 15 patients (A8344G in one, T8993C in two, and T8993G in 12), indicating that cultured lymphoblastoid cells are useful for elucidating the etiology of Leigh syndrome and that mtDNA mutations occured more frequently in Japanese patients with Leigh syndromeIn our study, five of 12 patients with T8993G mutations were associated with West syndrome and only patients with this mutation had West syndrome. These findings suggest that patients with Leigh syndrome associated West syndrome have a high possibility of defects due to T8993G mutations. Four patients with PDHC deficiency showed a reduced affinity for thiamine pyrophosphate, and thiamine treatment resulted in clinical improvements, indicating that these 4 patients have a thiamine-responsive PDHC deficiency and high doses of thiamine may be useful at the early stage of neurologic abnormalities in patients with Leigh syndrome due to this type of PDHC deficiency