线粒体脑肌病伴高乳酸血症及卒中样发作的发病机制及临床研究进展

Research Progression of Mitochondrial Encephalopathy,Lactic Acidosis,and Stroke-like Episodes in Pathogenesis and Clinic

线粒体脑肌病伴高乳酸血症及脑卒中样发作(MELAS)是在1984年前首次被提出的,该病主要是由线粒体基因组第3243号位点的腺嘌呤突变为鸟嘌呤(m.3243A>G)行导致。MELAS主要的神经系统表现为抽搐、脑卒中样发作和脑病,还包括一些其他症状如身材矮小、认知功能障碍、偏头痛、痴呆、心肌病、心脏传导阻滞和糖尿病等。本文主要从分子生物学角度讨论MELAS病的病因、诊断方式以及治疗手段的研究进展,着重阐述了细胞色素C氧化酶(COX)失调假说在MELAS病的发病机制中的作用。虽然MELAS病的治疗方法仍然有限,但是现有的和潜在的治疗方式值得探讨。

The syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes （MELAS） was initially described almost 25 years ago. This syndrome mostly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome. It is typified by characteristic neurological manifestations including seizures, stroke-like episodes and encephalopathy, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, dementia, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. The research progression of pathogenesis, diagnostic strategies and therapeutic tool of MELAS in molecular biology were reviewed. The hypothetical role of derangements to cytochrome-coxidase （COX） enzymatic function in driving the unique pathogenesis of MELAS were described. Although therapeutic options for MELAS remain limited, current and potential therapeutic modalities also could be considered.