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。发现缺陷30例(50%)，其中酶缺陷15例，丙酮酸脱氢酶复合体(PDHC)5例，呼吸链复合体I 4例，细胞色素C氧化酶(COX)6例。在15例患者中发现线粒体DNA(MtDNA)点突变，其中A8344G突变1例，T8993C突变2例，T8993G突变12例，提示培养的淋巴母细胞有助于阐明Leigh综合征的病因，mtDNA突变在日本Leigh综合征患者中更为常见。这些发现表明，Leigh综合征相关的West综合征患者存在T8993G突变导致缺陷的可能性很高。4名PDHC缺乏症患者对焦磷酸硫胺素的亲和力降低，硫胺素治疗导致临床改善，表明这4名患者患有硫胺素反应性PDHC缺乏症，在这种类型的PDHC缺乏症患者的早期神经异常阶段，高剂量硫胺素可能是有用的。

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