线粒体脑肌病伴有高乳酸血症和卒中样发作综合征的临床及基因突变分析

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes： clinical manifestations and gene mutation analysis

目的探讨线粒体脑肌病伴有高乳酸血症和卒中样发作综合征（MELAS）的临床及基因突变特征。方法对1例MELAS患者的临床表现、影像学、肌肉病理特点进行分析，并用PCR-RFLP结合基因测序方法进行线粒体基因突变分析。结果患者主要临床表现为发作性头痛和呕吐、反复卒中样发作、癫痫、运动不耐受、身材矮小、神经性耳聋、乳酸水平升高等。脑CT见双侧基底节多个钙化灶，MRI见枕叶异常信号，1H—MRS见T2WI异常信号区域有明显的乳酸峰，在T2正常信号区域也有小的乳酸峰。光镜及电镜肌肉病理检查未见明显的线粒体异常，基因检测显示mtDNAA3243G杂合突变。结论MELAS的诊断必须结合临床表现、影像学、病理学和基因突变检测等结果进行综合分析，病理学检查阴性不能否定MELAS的诊断，诊断MELAS应常规进行mtDNA突变分析。

Objective To investigate the characteristic clinical manifestations and gene mutations in mitoehondrial myopathy, cncephalopathy, lactic acidosis and stroke-like episodes （MELAS）. Methods The clinical manifestations, imaging data and muscle pathologies of a patient with MELAS were analyzed, and the mutations in the mitochondrial DNA were investigated using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and gene sequencing. Results MELAS was clinically characterized by such symptoms as recurrent headache and vomiting, stroke-like episodes, epilepsy, intolerance to exercise, short stature, nerve deafness and lactic acidosis. CT scan demonstrated bilateral basal ganglia calcification, and magnetic resonance imaging （MRI） showed abnormal signals in the occipital lobe. Proton magnetic resonance spectroscopy revealed a visible peak of lactic acid in the area with T2-weighted abnormal signals, while a low peak of lactic acid was identified in the area with T2-weighted normal signals. Muscle biopsy did not find any mitochondrial anomalies. A heterozygous A 3243G mutation in the mitochondrial DNA was found in this patient. Conclusion The diagnosis of MELAS relies on a comprehensive analysis of the clinical features, imaging findings, pathological results and genetic analysis. Normal pathological results do not rule out the possibility of MELAS. Mitochondrial DNA mutation analysis should be carried out as a routine procedure for identifying MELAS.