A new mitochondria-related disease showing myopathy with episodic hyper-creatine kinase-emia
A new mitochondria-related disease showing myopathy with episodic hyper-creatine kinase-emia
复制标题
一种新的线粒体相关疾病，表现为伴有阵发性高肌酸激酶血症的肌病
作者：
Okamoto Y;Higuchi I;Sakiyama Y;et al
目的阐明线粒体DNA（mtDNA）改变与线粒体疾病特征性症状（即发作性高肌酸激酶（CK）血症和轻度myopathy.MethodsWe从586例疑似线粒体疾病患者中选择9例mtDNA np 8291改变患者，并对其进行临床、病理和遗传学评估。这9例患者有未确诊的线粒体肌病与发作性高CK-血症，所有表现出类似的症状和progress.ResultsPatients有轻度肌无力和发作性高CK-血症引发的感染或药物。9名患者中有5名最初被诊断为其他疾病，如重症肌无力，多发性肌炎，病毒性肌炎和药物诱导的肌病，因为这些疾病是急性或亚急性的，9名患者显示出相同的16个mtDNA改变，据报道这些改变是非病理性多态性。肌肉活检显示不规则的红色纤维、高表达琥珀酸脱氢酶染色纤维和细胞色素氧化酶缺陷纤维。由于他们的线粒体序列数据几乎相同，并且9名患者居住在日本相隔很远的城市，这些改变可能来自单一来源。解释这些发现表明，轻度肌病伴发作性高CK血症与16种mtDNA改变中的一些改变或至少与线粒体有关，可能是一种新型线粒体疾病。因此，我们建议将这种疾病命名为“线粒体肌病伴发作性高CK血症（MIMECK）”。这些改变可能会同时起作用，并可能改变药物或其他环境因素的影响。我们相信这些发现提供了一个新的方面线粒体疾病的发病机制的见解。神经网络2011;70：486-492。
ObjectiveTo elucidate the relationship between mitochondrial DNA (mtDNA) alterations and a mitochondrial disease with a distinct combination of characteristic symptoms, namely episodic hyper‐creatine kinase (CK)‐emia and mild myopathy.MethodsWe selected 9 patients with mtDNA np8291 alteration from 586 patients suspected to have a mitochondrial disease, and assessed them clinically, pathologically, and genetically. These 9 patients had undiagnosed mitochondrial myopathy with episodic hyper‐CK‐emia, all showing similar symptoms and progression.ResultsPatients had mild muscle weakness and episodic hyper‐CK‐emia triggered by infections or drugs. Five of 9 patients were initially diagnosed with other conditions, such as myasthenia gravis, polymyositis, viral myositis, and drug‐induced myopathy, because these conditions were acute or subacute, and 9 patients showed the same 16 mtDNA alterations, which have been reported to be nonpathological polymorphisms. Muscle biopsy revealed ragged‐red fibers, highly expressed succinate dehydrogenase staining fibers, and cytochromecoxidase–deficient fibers. Because their mitochondrial sequence data was almost the same, and 9 patients live in widely separated cities in Japan, the alterations may have arisen from a single source.InterpretationThese findings suggest that mild myopathy with episodic hyper‐CK‐emia associated with some of the 16 mtDNA alterations or at least with their mitochondria, could be a novel mitochondrial disease. Therefore, we propose that this disease be named as “mitochondrial myopathy with episodic hyper‐CK‐emia (MIMECK).” These alterations could work concomitantly and probably modify the impact of medications or other environmental factors. We believe these findings provide an insight into a novel aspect of mitochondrial disease pathogenesis. ANN NEUROL 2011;70: 486–492.