Electron microscopic findings are an important aid for diagnosing mitochondrial cardiomyopathy with mitochondrial DNA mutation 3243A>G.
Electron microscopic findings are an important aid for diagnosing mitochondrial cardiomyopathy with mitochondrial DNA mutation 3243A>G.
复制标题
电镜检查结果对于诊断线粒体 DNA 突变 3243A>G 的线粒体心肌病有重要帮助。
DOI：
10.1161/circheartfailure.116.003283
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Saito Y.
中科院分区：
文献类型：
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作者：
Takemura G;Onoue K;Kashimura T;Kanamori H;Okada H;Tsujimoto A;Miyazaki N;Nakano T;Sakaguchi Y;Saito Y.
线粒体疾病可由线粒体或核DNA缺陷引起，但mtDNA突变是成人最常见的原因。在这些突变中，m. 3243A >g突变（MTTL）首次在线粒体脑肌病、乳酸酸中毒和卒中样发作综合征患者中被发现。2该突变位于编码tRNALeu的基因上，导致蛋白质合成受损和电子传递链功能障碍。2 40%有症状的个体有心肌病，通常是左心室肥厚伴运动不足，3然而，当患者表现出线粒体疾病的典型表型时，这一点经常被忽视。患者（病例1）为一名60岁男性，因充血性心力衰竭导致呼吸困难而入住奈良医科大学医院。他患有高血压和糖尿病近10年，听力困难2年。他的母亲也患有糖尿病，并被诊断为在她的mtDNA 3243位（m. 3243A> G）有a到G的转变。超声心动图检查显示左心室弥漫性肥厚和功能减退。左心导管检查未见明显冠状动脉病变。心内膜活检显示心肌细胞明显空泡变性（图1）。其中一位作者（岐阜大学的GT）对活检标本进行了电镜检查，发现线粒体异常，包括数量明显增加，但大小差异很大，经常脱落，畸形，糖原沉积，不规则运动，收缩或嵴部分退变（图2）。背景糖原沉积也增加。因此，超微结构证据提示线粒体心肌病。此外，遗传分析显示，在他的母亲身上观察到同样的异常：m. 3243A> G. 6年后，另一个心内膜活检标本从新潟大学医院送到朝日大学GT（从岐阜大学转移）进行电子检测
Mitochondrial disease can be caused by defects in either mitochondrial or nuclear DNA, but mtDNA mutations are the most common cause in adult. 1 Among these mutations, m. 3243A> G mutation (MTTL) was first identified in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome. 2 The mutation is located in the gene encoding tRNALeu and results in impaired protein synthesis and electron transport chain dysfunction. 2 Cardiomyopathy is seen in 40% of the symptomatic individuals, usually left ventricular hypertrophy with hypokinesis, 3 which however is often overlooked when the patients show few phenotypes typical for mitochondrial disease.The patient (case 1) was a 60-year-old man admitted to Nara Medical University Hospital because of dyspnea due to congestive heart failure. He had hypertension and diabetes mellitus for nearly 10 years and had been hard of hearing for 2 years. His mother also had diabetes mellitus and was diagnosed with an A-to-G transition at position 3243 of her mtDNA (m. 3243A> G). Echocardiographic examination of the patient revealed diffuse hypertrophy and hypofunction of the left ventricle. Left heart catheterization showed no significant coronary artery disease. Endomyocardial biopsy showed marked vacuolar degeneration of the cardiomyocytes (Figure 1). Electron microscopic examination of the biopsy specimen by one of the authors (GT at Gifu University) revealed mitochondrial abnormalities that included a marked increase in their number but with great differences in size, frequent dropping out, deformity, glycogen deposits, irregular running, shrinkage, or partial degeneration of the cristae (Figure 2). Background glycogen deposits were also increased. The ultrastructural evidence, thus, suggested mitochondrial cardiomyopathy. Moreover, genetic analysis revealed the same abnormality observed in his mother: m. 3243A> G. Six years later, another endomyocardial biopsy specimen was sent from Niigata University Hospital to GT at Asahi University (moved from Gifu University) for electron