线粒体呼吸链酶缺陷临床分析

Clinical Analysis of Mitochondrial Respiratory Chain Enzyme Deficiency in Children : Report of 7 Cases

目的探讨经线粒体呼吸链酶复合物活性测定确诊的非综合征型线粒体病患儿的临床特点。方法选择2010年3月至2011年4月在首都儿科研究所附属儿童医院神经内科就诊的疑似线粒体病、经呼吸酶链复合物Ⅰ～Ⅴ活性检测确诊为非综合征型线粒体病的7例患儿为研究对象。其中,男性患儿为6例,女性为1例(本研究遵循的程序符合本院人体试验委员会制定的伦理学标准,得到该委员会批准,并征得患儿监护人的知情同意)。对其外周血白细胞呼吸链酶复合物Ⅰ～Ⅳ,ATP合成酶(复合物Ⅴ)活性进行测定,并对其临床资料进行回顾性分析。结果①感染后出现智力倒退为5例,合并惊厥发作为4例、瘫痪为6例;耳聋、共济失调各2例,合并垂体前叶功能低下/发作性低血糖为1例;肌力及肌张力减低为7例。头颅磁共振检查异常为6例,脑电图异常为5例,肌电图异常为3例。血乳酸轻度升高为3例,心肌酶谱异常为2例。②常规线粒体基因筛查均呈阴性。③线粒体呼吸链酶复合物缺陷:复合物Ⅱ缺陷为2例,复合物Ⅰ,Ⅳ缺陷各为1例,复合物Ⅰ+Ⅲ缺陷为2例,复合物Ⅱ+Ⅴ缺陷为1例。结论儿童线粒体呼吸链酶缺陷可缺乏特异性的神经系统症状,表现为多系统广泛受累,且常规线粒体基因筛查呈阴性,进行外周血线粒体呼吸链酶复合物活性测定,有助于确诊非综合征型线粒体病。

Objective To investigate the clinical features of the non-syndromic mitochondrial disease in children which were identified by mitochondrial respiratory chain enzyme complex activity assay. Methods From March 2010 to April 2011, seven children who were diagnosed as non-syndromic mitochondrial disease were included into this study. The enzyme activity of respiratory chain enzyme complexes （ I-IV ） and ATP synthase （complex V ） in peripheral blood leukocytes of 7 children were determined. All the children whose routine screening of mitochondrial genes were negative. Children＇s clinical data were retrospectively analyzed. Results ①There were intelligence backwards after infection in 5 cases, combined seizures in 4 cases, paralysis in 6 cases; deafness, ataxia in 2 cases, combining anterior pituitary hypofunction/episodes of hypoglycemia in 1 case; myodynamia and hypomyotonia in 7 cases. The findings of brain MRI were abnormal in 6 cases, the findings of electroencephalogram （EEG） were abnormal in 5 cases and abnormal findings of electromyography （EMG） in 3 cases. Blood lactate increased slightly in 3 cases, the level of myocardial enzyme were abnormal in 2 cases. ②Conventional mitochondrial genes screening was negative.③ 4 childen had isolated complex defects： complex II deficiency （2 cases）, complex deficiency of I or IV （1 case, respectively）; 3 cases were found to have combined deficiencies： 2 cases had combined deficiencies of complex I and III , 1 case had combined deficiencies of complex II and V. Conclusions Mitochondrial respiratory chain enzyme deficiency in children may present non-specific neurological symptoms, the clinical features were extensive involvement of multi-system, and regular screening of mitochondrial gene was negative, the mitochondrial respiratory chain enzyme activity assay of peripheral leukocyte may help to identify the non-syndromic mitochondrial disease.