ND3基因突变导致的线粒体脑肌病重叠综合征二例

Two cases of mitochondrial encephalomyopathy caused by ND3 gene mutation

目的孤立的线粒体电子传递链复合物Ⅰ缺陷是线粒体病常见的原因之一,可导致几种独特的临床综合征。方法本文报道2例NADH脱氢酶(ND)基因突变导致的线粒体脑肌病的临床资料,分析该2例线粒体脑肌病患者的临床表现,头颅影像学,血乳酸,血生化,血氨基酸,尿有机酸等,脑电图(EEG),肌电图(EMG)和神经传导速度,以及线粒体全基因二代测序和线粒体相关核基因的检查。结果例1患者部分症状符合线粒体脑肌病伴乳酸血症和卒中样发作(MELAS),部分症状符合伴破碎红纤维肌阵挛癫痫(MERRF)。该患者头颅MRI除MELAS常见的皮质病变外,还可见中脑和四叠体对称性异常信号,符合Leigh综合征(LS)影像学表现。线粒体基因二代测序发现MT ND3,10158T>C突变。例2患者临床表现完全符合MELAS的临床特征,但头颅MRI可见中脑红核双侧对称性病变,又符合LS的影像学特征。线粒体全基因二代测序发现ND3,10191T>C突变。结论对于难以解释的神经系统症状和体征,尤其有多系统受累表现,即使临床表现不符合某种独特的线粒体病综合征,也要提高警惕,避免漏诊。

Objective Isolated complex 1 deficiency is one of the most common reasons of mitochondrialdisease, which can result in several distinct clinical syndromes. Two cases of mitochondrial encephalomyopathy causedby NADH dehydrogenase gene mutation were reported. Method Two cases of mitochondrial encephalomyopathywere analyzed including clinical features, lactic acid, biochemistry and amino acid of blood, organic acid of urine, etc.Meanwhile, the results of neurophysiological examinations and gene tests were also analyzed. Results Some symptomsof case 1 conformed to MELAS, while the others were accorded with MERRF. The MRI features of case 1 disclosedsymmetric abnormal signals of midbrain and quadrigemina conforming to Leigh's syndrome except that the commoncortical lesions of MELAS were disclosed at the same time. 10158T>C point mutation of mitochondrial gene ND3 wasfound through next generation sequencing. Although the clinical presentations of case 2 conformed to MELAS, MRIfound symmetric lesions of midbrain which indicated Leigh's syndrome. 10191T>C point mutation was found in case2.Conclusion Attention should be paid to the patients with neurological symptoms and signs without found reasons,especially when multisystem were affected, even when the clinical findings may be not characteristic for mitochondrialdisease.