背景:原发性线粒体疾病(PMD)是能量代谢最常见的先天性错误,合并患病率为4300中的1。它们可以起因于核DNA(nDNA)或线粒体DNA(mtDNA)中的突变。这些疾病是多系统的,主要影响高能量需求的组织,如肌肉和中枢神经系统(CNS)。在中枢神经系统受累的许多临床特征中,帕金森病是PMD中最常见的运动障碍之一。
方法:这篇综述提供了线粒体帕金森病领域最新进展的实用教育概述,从病理生理学和遗传病因到表型和诊断。
结果:mtDNA维持和线粒体动力学改变代表了线粒体帕金森病的主要机制。它可以孤立地存在,与其他运动障碍或,更常见的是,作为多系统表型的一部分。几个核编码基因的突变(即,POLG,TWNK,SPG7和OPA1)和,很少,mtDNA突变,负责线粒体帕金森病。进行性外部视神经麻痹和视神经萎缩可能指导遗传病因鉴定。
结论:需要一种全面的深层表型方法来诊断线粒体帕金森病,缺乏独特的临床特征,并举例说明了PMD的复杂基因型-表型相互作用。
BACKGROUND: Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). These disorders are multisystemic and mainly affect high energy-demanding tissues, such as muscle and the central nervous system (CNS). Among many clinical features of CNS involvement, parkinsonism is one of the most common movement disorders in PMDs.
METHODS: This review provides a pragmatic educational overview of the most recent advances in the field of mitochondrial parkinsonism, from pathophysiology and genetic etiologies to phenotype and diagnosis.
RESULTS: mtDNA maintenance and mitochondrial dynamics alterations represent the principal mechanisms underlying mitochondrial parkinsonism. It can be present in isolation, alongside other movement disorders or, more commonly, as part of a multisystemic phenotype. Mutations in several nuclear-encoded genes (ie, POLG, TWNK, SPG7, and OPA1) and, more rarely, mtDNA mutations, are responsible for mitochondrial parkinsonism. Progressive external opthalmoplegia and optic atrophy may guide genetic etiology identification.
CONCLUSIONS: A comprehensive deep-phenotyping approach is needed to reach a diagnosis of mitochondrial parkinsonism, which lacks distinctive clinical features and exemplifies the intricate genotype-phenotype interplay of PMDs.