Lombes A, Bonilla E, Dimauro S
H Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Rev Neurol (Paris). 1989;145(10):671-89.
Increasingly numerous studies are being devoted to mitochondrial diseases, notably those which involve the neuromuscular system. Our knowledge and understanding of these diseases is progressing rapidly. We owe to Luft et al. (1962) the first description of this type of diseases. Their patient, a woman, presented with clinical symptoms suggestive of mitochondrial dysfunction, major histological abnormalities of skeletal muscle mitochondria and defective oxidative phosphorylation coupling clearly demonstrated in mitochondria isolated from muscle. This clinical, histological and biochemical triad led to the definition of mitochondrial myopathies. Subsequently, the triad was seldom encountered, and most mitochondrial myopathies were primarily defined by the presence of morphological abnormalities of muscle mitochondria. This review deals with the morphological, clinical, biochemical and genetic aspects of mitochondrial encephalomyopathies. The various morphological abnormalities of mitochondria are described. These are not specific of any particular disease. They may be present in some non-mitochondrial diseases and may be lacking in diseases due to specific defects of mitochondrial enzymes (e.g. carnitine palmityl-transferase or pyruvate dehydrogenase). The clinical classification of mitochondrial encephalomyopathies is discussed. There are two main schools of thought: the "lumpers" do not recognize specific syndromes within the spectrum of mitochondrial "cytopathies", the "splitters" try to identify specific syndromes while recognizing the existence of borderline cases. The following syndromes are described: chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), MERRF syndrome (myoclonic epilepsy with ragged-red fibers), MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and Leigh and Alpers syndromes. The biochemical classification comprises five types of abnormalities: defects of transport through the mitochondrial membrane, of substrate utilization, of Krebs' cycle, of oxidative phosphorylation and of various complexes of the respiratory chain. The clinical pictures corresponding to these defects are briefly described. The genetic aspects of these diseases are especially interesting because mitochondria have their own genome coding for thirteen proteins, all of them belonging to the respiratory chain. Genetic mitochondrial diseases may result from alterations of the nuclear genome, which are transmitted by mendelian inheritance, but they may also be due to alterations of the mitochondrial genome and transmitted by non-mandelian "maternal" heredity. A few examples are discussed, including Leber's optic atrophy and MERRF syndrome. (ABSTRACT TRUNCATED AT 400 WORDS)
越来越多的研究致力于线粒体疾病，尤其是那些累及神经肌肉系统的疾病。我们对这些疾病的认识和理解正在迅速发展。线粒体疾病的首次描述归功于卢夫特等人（1962年）。他们的患者是一名女性，表现出提示线粒体功能障碍的临床症状、骨骼肌线粒体明显的组织学异常以及从肌肉分离的线粒体中清楚显示的氧化磷酸化偶联缺陷。这种临床、组织学和生化三联征导致了线粒体肌病的定义。随后，很少遇到这种三联征，大多数线粒体肌病主要通过肌肉线粒体形态异常来定义。本综述涉及线粒体脑肌病的形态学、临床、生化和遗传学方面。描述了线粒体的各种形态异常。这些异常并非任何特定疾病所特有。它们可能存在于一些非线粒体疾病中，也可能在因线粒体酶特定缺陷（如肉碱棕榈酰转移酶或丙酮酸脱氢酶）导致的疾病中不存在。讨论了线粒体脑肌病的临床分类。主要有两种观点：“合并派”不承认线粒体“细胞病”范围内的特定综合征，“细分派”试图识别特定综合征，同时承认存在临界病例。描述了以下综合征：慢性进行性眼外肌麻痹（CPEO）、卡恩斯 - 塞尔综合征（KSS）、肌阵挛性癫痫伴破碎红纤维综合征（MERRF）、线粒体肌病、脑病、乳酸酸中毒、卒中样发作综合征（MELAS）以及 Leigh 综合征和阿尔珀斯综合征。生化分类包括五种异常类型：线粒体膜转运缺陷、底物利用缺陷、三羧酸循环缺陷、氧化磷酸化缺陷以及呼吸链各种复合物缺陷。简要描述了与这些缺陷相对应的临床症状。这些疾病的遗传学方面尤其有趣，因为线粒体有自己的基因组，编码13种蛋白质，所有这些蛋白质都属于呼吸链。遗传性线粒体疾病可能源于核基因组的改变，通过孟德尔遗传传递，但也可能是由于线粒体基因组的改变，并通过非孟德尔式“母系”遗传传递。讨论了一些例子，包括莱伯遗传性视神经萎缩和MERRF综合征。（摘要截取自400字）
