线粒体基因14453G>A突变所致线粒体脑肌病伴高乳酸血症和卒中样发作1例并文献复习

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes caused by mitochondrial DNA 14453G>A mutation:a case report and literature review

目的探讨m.14453G>A突变所致线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)患者的临床及影像学特点。方法报道2021年10月12日就诊于哈尔滨医科大学附属第一医院的1例线粒体基因14453G>A(m.14453G>A)突变所致的MELAS患者,同时系统性回顾国内外文献中所发表的m.14453G>A突变所致的MELAS及Leigh综合征(LS)的病例,对其进行总结分析和比较。结果患者女性,13岁起无明显诱因出现抽搐发作,伴有情绪障碍及记忆力下降。磁共振成像见额叶、顶叶、枕叶、颞叶及小脑病变。曾考虑为自身免疫性脑炎及可逆性后部白质脑病综合征。通过二代测序对患者行线粒体全基因组检测,在ND6基因上发现变异比率为17%的m.14453G>A突变。根据临床表现、影像学检查及基因检测结果诊断为MELAS。以“m.14453G>A”为检索词对国内外文献进行检索,筛选临床资料完整者。共检索到符合条件的国外文献5篇、国内文献3篇,共报道m.14453G>A突变11例(含本例)。诊断MELAS 5例,LS 6例。11例患者中青少年及成年发病者,MRI上多累及皮质及皮质下白质,常考虑为MELAS;婴幼儿发病者,MRI上多累及基底节区、丘脑及脑干,考虑为LS。结论m.14453G>A突变导致的临床表型存在异质性,可引起MELAS、LS。m.14453G>A突变的临床表型与发病年龄及病变部位存在一定的相关性。

Objective To explore the clinical and imaging characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)caused by mitochondrial DNA 14453G>A(m.14453G>A)mutation.Methods A case of MELAS caused by m.14453G>A mutation in the First Affiliated Hospital of Harbin Medical University on October 12,2021 was reported.At the same time,the reported cases of MELAS and Leigh syndrome(LS)caused by the m.14453G>A mutation were reviewed.This enabled a comprehensive summarization,analysis,and comparison of these cases.Results The patient was a female.She has suffered from the disease since 13-year old with seizures,accompanied by the disturbance of mood and the loss of memory.Brain magnetic resonance imaging findings consisted of lesions in frontal,parietal,occipital,temporal lobe and cerebellar.The patient was initially considered with autoimmune encephalitis and posterior reversible encephalopathy syndrome.Since direct sequencing of the complete mitochondrial genome from blood of the patient revealed m.14453G>A mutation in ND6 gene,and the mutation rate was 17.0%,the patient eventually diagnosed with MELAS based on clinical manifestations,imaging examinations,and genetic testing results.Using"m.14453G>A"as the search term,the relevant literature in China and abroad was retrieved and those with complete clinical data were identified.A total of 11 cases of m.14453G>A mutation including this case were reported,of whom 5 patients were diagnosed as MELAS,and 6 patients were diagnosed as LS.Among the 11 patients,those being adolescent or adult and with lesions in the cortex and subcortical white matter were probably be MELAS;those being infant or young child and with lesions in basal ganglia,thalamus and brainstem could be LS.Conclusions Mitochondrial disease caused by m.14453G>A gene mutation shows a great heterogeneity,which can cause MELAS and LS.The clinical phenotype of the m.14453G>A mutation may be related to the age of onset and lesion′s location.