摘要：

目的 总结10例晚发型线粒体脑肌病伴高乳酸血症和卒中样发作（MELAS）患者的临床、病理及基因突变特点。方法与结果 回顾分析2007年1月至2018年12月共10例晚发型MELAS患者的临床资料，8例患者行骨骼肌组织活检术。聚合酶链反应-限制性片段长度多态性和线粒体DNA （mtDNA）全长测序法进行mtDNA突变筛查；焦磷酸测序法检测部分患者血液m.3243A > G突变比例。结果显示，10例患者首次脑卒中样发作的年龄为40~67岁，其主要表现包括癫发作、失语、头痛、痴呆、精神障碍、肢体轻瘫及视力下降，既往糖尿病5例、神经性耳聋6例、高血压3例、脑梗死2例。6例患者有母系遗传的糖尿病家族史，2例有MELAS家族史。辅助检查可见6例有高脂血症，6例有颈动脉粥样硬化，1例有右颈内动脉及大脑中动脉狭窄。头部MRI显示累及1个或多个脑叶的皮质病变，4例同时存在脑干及基底节区多发缺血灶。7例肌肉组织活检发现破碎红纤维及琥珀酸脱氢酶深染血管，1例未见明显异常。基因分析显示，10例患者均携带mtDNA突变，9例为m.3243A > G突变，1例为m.10191T > C突变。7例m.3243A > G突变患者血液中突变比例为9%～33%。结论 晚发型MELAS患者的临床表型与经典型患者无明显差异，但发病年龄晚，并可合并多种脑血管危险因素及大动脉粥样硬化。m.3243A > G突变为本组晚发型MELAS患者的热点突变，但血液中突变比例较低。

关键词: MELAS综合征, 晚发性障碍, DNA,线粒体, 突变

Abstract:

Objective To summarize the clinical, pathological and genetic features of 10 patients with late-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Methods and Results The clinical data of 10 patients with late-onset MELAS were retrospectively analyzed from January 2007 to December 2018. Muscle biopsy was performed in 8 cases. Polymerase chain reaction-fragment length polymorphism (PCR-RFLP) analysis and whole sequencing of mitochondrial DNA (mtDNA) were used to screen mtDNA mutations, and the mutation load of m.3243A > G in blood was detected by pyrophosphate sequencing. The onset age of the first stroke-like episodes were 40-67 years old in all patients. The main manifestations included epilepsy, aphasia, headache, dementia, mental disorder, limb paralysis and visual impairment. Past history revealed 5 cases with diabetes mellitus, 6 with deafness, 3 with hypertension and 2 with stroke. Six patients had a family history of maternally inherited diabetic mellitus, and 2 had a family history of MELAS. Laboratory examination revealed 6 cases with hyperlipidemia, 6 with carotid atherosclerosis, 1 with stenosis of right internal carotid artery and middle cerebral artery. Brain MRI showed cortex lesions involving one or more lobes in all patients, and 4 cases also had multiple infarctions in brainstem and basal ganglia. Muscle biopsy demonstrated ragged red fiber (RRF) and strongly succinate dehydrogenase-stained vessels (SSVs) in all of 8 patients except one. Genetic analysis identified 9 cases with m.3243A > G, and 1 with m.10191T > C mutation. The blood mutation load of m.3243A > G was 9%-33% in 7 cases. Conclusions The clinical phenotype of patients with late-onset MELAS was not significantly different from that of typical patients. However, the age of onset in late-onset MELAS was late, and it could be complicated with a variety of cerebrovascular risk factors and atherosclerosis. The hotspot mutation of this group of late-onset MELAS patients was m.3243A > G, but the mutation rate in blood was low.

Key words: MELAS syndrome, Late onset disorders, DNA,mitochondrial, Mutation