Radelfahr Florentine, Klopstock Thomas
Ludwig-Maximilians-Universität München, Friedrich- Baur-Institut der Neurologischen Klinik.
Fortschr Neurol Psychiatr. 2018 Sep;86(9):584-591. doi: 10.1055/a-0621-9255. Epub 2018 Sep 24.
Mitochondrial diseases (MD) represent a heterogenous group of disorders and syndromes caused either by mutations of the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). They belong to the most frequent neurogenetic diseases. The spectrum of clinical manifestations is very broad ranging from mild subclinical presentations to rapidly progressive debilitating conditions with reduced life expectancy. Mitochondrial dysfunction can affect any organ of the body; the clinical presentation is often most severe in tissues with high energy demands. The most common MD are Leber's Hereditary Optic Neuropathy (LHON), Chronic Progressive External Ophthalmoplegia (CPEO), Kearns-Sayre Syndrome (KSS), Mitochondrial Myopathy (MM) and Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike episodes (MELAS). In the last couple of years, genetics have become more and more important for the diagnosis of MD. The majority of syndromes presents with a characteristic combination of clinical and laboratory findings which should guide the selection of tissues (blood cells, fibroblasts, urothelial cells or muscle) and methods for targeted genetic testing. Therapeutic approaches to MD include pharmacological stimulation of mitochondrial metabolism, supplementation, symptomatic treatment, assistive devices and physiotherapy. Moreover, strict anti-epileptic therapy and treatment or prevention of stroke-like episodes are very important to prevent complications. In contrast, some medication should be avoided for its direct or indirect depressing effect on mitochondrial function. This article provides an introduction to mitochondrial diseases, an overview of the most common syndromes and an update on established and new therapeutic approaches.
线粒体疾病(MD)是一组由线粒体DNA(mtDNA)或核DNA(nDNA)突变引起的异质性疾病和综合征。它们属于最常见的神经遗传性疾病。临床表现范围非常广泛,从轻度亚临床症状到迅速进展的使人衰弱的病症,预期寿命缩短。线粒体功能障碍可影响身体的任何器官;在能量需求高的组织中,临床表现通常最为严重。最常见的线粒体疾病有Leber遗传性视神经病变(LHON)、慢性进行性外眼肌麻痹(CPEO)、卡恩斯-塞尔综合征(KSS)、线粒体肌病(MM)以及线粒体脑肌病、乳酸酸中毒和卒中样发作(MELAS)。在过去几年中,遗传学在MD的诊断中变得越来越重要。大多数综合征表现出临床和实验室检查结果的特征性组合,这应指导组织(血细胞、成纤维细胞、尿路上皮细胞或肌肉)的选择以及靶向基因检测的方法。MD的治疗方法包括线粒体代谢的药物刺激、补充、对症治疗、辅助装置和物理治疗。此外,严格的抗癫痫治疗以及对卒中样发作的治疗或预防对于预防并发症非常重要。相比之下,一些药物因其对线粒体功能有直接或间接的抑制作用而应避免使用。本文介绍了线粒体疾病,概述了最常见的综合征,并更新了已有的和新的治疗方法。