Service de neurologie, CHU d'Angers, 4, rue Larrey, 49033 Angers, France; CNRS UMR 6214, 4, rue Larrey, 49033 Angers, France; Inserm UMR 1083, 4, rue Larrey, 49033 Angers, France.
Service de neurologie, CHU d'Angers, 4, rue Larrey, 49033 Angers, France.
Rev Neurol (Paris). 2014 May;170(5):366-74. doi: 10.1016/j.neurol.2013.11.005. Epub 2014 Apr 24.
Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes.
线粒体疾病（MIDs）常导致程度不一的神经病变。引起周围神经病（PNP）的线粒体疾病可能是由于线粒体 DNA（mtDNA）的突变，如 MERRF 和 MELAS 综合征，也可能是由于核基因突变。mtDNA 的继发异常（如肌肉 mtDNA 的多处缺失）可能是由于核基因突变导致的线粒体功能障碍引起的，这种情况见于几种由于 mtDNA 维持障碍引起的综合征，如感觉运动性共济失调神经病、构音障碍和眼肌麻痹（SANDO），是由于编码 mtDNA 聚合酶（DNA 聚合酶γ）催化亚基的 POLG 基因的隐性突变引起的，或线粒体神经胃肠脑肌病（MNGIE），是由于编码胸苷磷酸化酶的 TYMP 基因的隐性突变引起的。近年来越来越多的证据表明，线粒体生物能学和动力学可能在轴索性腓骨肌萎缩症（CMT2）中出现功能障碍，这些机制可能是不同 CMT2 致病基因之间的共同联系。
