线粒体DNA A3243G点突变的临床异质性表现

目的探讨线粒体DNA A3243G点突变的临床表现特点.方法以25例临床怀疑为线粒体病,经血或肌肉线粒体DNA检查证实有A3243G点突变的线粒体脑肌病患者为研究对象,分析其临床表现、脑影像学特点、血乳酸水平和肌肉病理检查结果.结果基因检测证实25例患者均存在比例不同的线粒体DNA A3243G点突变,但临床表型有很大不同,其中19例为线粒体脑肌病伴乳酸血症和卒中样发作(MELAS),2例为无法分类的线粒体脑病,2例为松软儿,1例为Kearns-Sayer综合征(KSS),1例为线粒体胃肠肌病.大部分患者脑影像学检查可见病灶,肌肉活检可见蓬毛样红纤维改变,所有患者均有血乳酸水平增高.结论线粒体DNA A3243G点突变的临床表现和脑影像学均呈高度的异质性.对表现为多系统受累的患者,如果同时合并高乳酸血症,就应考虑线粒体病的可能,应进行线粒体DNA突变的检查以明确诊断.

Phenotype heterogeneity associated with mitochondrial DNA A3243G mutation

Objective To discuss the clinical characteristics associated with mitochondrial DNA A3243G mutation. Methods Clinical manifestations as well as results of brain CT and/or MRI scanning, blood level of lactic acid and muscle biopsy results of 25 mitochondrial encephalomyopathies patients whose A3243G mutations were analyzed. Results Although all of the 25 patients carried mtDNA A3243G point mutation, their clinical manifestations varied greatly. Among them, there were 19 cases of mitochon-drial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS), 2 cases of encephalopathies which could not be classified into any specific type, 2 cases of floppy infants, one case of kearns-sayer syndrome(KSS)and one case of mitochondrial entero-myopathy. Most patients showed abnormal cranial radiological findings and ragged-red-fibers on muscle biopsies. Elevation of blood lactic acid was notably found in all of the 25 patients. Conclusions Significant variations in clinical manifestation and brain images are the prominent features in patients with A3243G mutation. Mitochondrial diseases should be considered in patients with multiple organ involvement and elevated serum lactic acid mtDNA mutation examination is necessary for the diagnosis of mitochondrial diseases.