Liang Christina, Ahmad Kate, Sue Carolyn M
Department of Neurology, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.
Department of Neurology, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia; Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and the University of Sydney, St. Leonards, New South Wales 2065, Australia.
Biochim Biophys Acta. 2014 Apr;1840(4):1360-7. doi: 10.1016/j.bbagen.2013.10.040. Epub 2013 Nov 13.
The diagnosis of mitochondrial disease requires a complex synthesis of clinical, biochemical, histological, and genetic investigations. An expanding number of mitochondrial diseases are being recognized, despite their phenotypic diversity, largely due to improvements in methods to detect mutations in affected individuals and the discovery of genes contributing to mitochondrial function. Improved understanding of the investigational pitfalls and the development of new laboratory methodologies that lead to a molecular diagnosis have necessitated the field to rapidly adopt changes to its diagnostic approach.
We review the clinical, investigational and genetic challenges that have resulted in shifts to the way we define and diagnose mitochondrial disease. Incorporation of changes, including the use of fibroblast growth factor 21 (FGF-21) and next generation sequencing techniques, may allow affected patients access to earlier molecular diagnosis and management.
There have been important shifts in the diagnostic paradigm for mitochondrial disease. Diagnosis of mitochondrial disease is no longer reliant on muscle biopsy alone, but should include clinical assessment accompanied by the use of serological biomarkers and genetic analysis. Because affected patients will be defined on a molecular basis, oligosymptomatic mutation carriers should be included in the spectrum of mitochondrial disease. Use of new techniques such as the measurement of serum FGF-21 levels and next-generation-sequencing protocols should simplify the diagnosis of mitochondrial disease.
Improvements in the diagnostic pathway for mitochondrial disease will result in earlier, cheaper and more accurate methods to identify patients with mitochondrial disease. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.
线粒体疾病的诊断需要综合临床、生化、组织学和遗传学等多方面的检查。尽管线粒体疾病的表型具有多样性，但目前被识别出的此类疾病数量仍在不断增加，这主要归功于检测患者突变方法的改进以及对线粒体功能相关基因的发现。对研究陷阱的深入理解以及能够实现分子诊断的新实验室方法的发展，使得该领域必须迅速调整其诊断方法。
我们回顾了导致线粒体疾病定义和诊断方式发生转变的临床、研究及遗传方面的挑战。纳入一些变化，包括使用成纤维细胞生长因子21（FGF - 21）和下一代测序技术，可能会使受影响的患者能够更早地获得分子诊断和治疗。
线粒体疾病的诊断模式发生了重要转变。线粒体疾病的诊断不再仅仅依赖于肌肉活检，而应包括临床评估，并结合血清生物标志物的使用和遗传分析。由于将在分子基础上对受影响的患者进行定义，因此寡症状突变携带者也应纳入线粒体疾病的范畴。使用诸如测量血清FGF - 21水平和下一代测序方案等新技术，应能简化线粒体疾病的诊断。
线粒体疾病诊断途径的改进将带来更早、更便宜且更准确的方法来识别线粒体疾病患者。本文是名为《线粒体研究前沿》特刊的一部分。
