Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
Handb Clin Neurol. 2023;195:563-585. doi: 10.1016/B978-0-323-98818-6.00025-X.
Mitochondrial dysfunction, especially perturbation of oxidative phosphorylation and adenosine triphosphate (ATP) generation, disrupts cellular homeostasis and is a surprisingly frequent cause of central and peripheral nervous system pathology. Mitochondrial disease is an umbrella term that encompasses a host of clinical syndromes and features caused by in excess of 300 different genetic defects affecting the mitochondrial and nuclear genomes. Patients with mitochondrial disease can present at any age, ranging from neonatal onset to late adult life, with variable organ involvement and neurological manifestations including neurodevelopmental delay, seizures, stroke-like episodes, movement disorders, optic neuropathy, myopathy, and neuropathy. Until relatively recently, analysis of skeletal muscle biopsy was the focus of diagnostic algorithms, but step-changes in the scope and availability of next-generation sequencing technology and multiomics analysis have revolutionized mitochondrial disease diagnosis. Currently, there is no specific therapy for most types of mitochondrial disease, although clinical trials research in the field is gathering momentum. In that context, active management of epilepsy, stroke-like episodes, dystonia, brainstem dysfunction, and Parkinsonism are all the more important in improving patient quality of life and reducing mortality.
线粒体功能障碍，特别是氧化磷酸化和三磷酸腺苷 (ATP) 生成的紊乱，破坏了细胞的内稳态，是中枢和周围神经系统病理的一个惊人的常见原因。线粒体疾病是一个总称，包括由超过 300 种不同的遗传缺陷引起的多种临床综合征和特征，这些缺陷影响线粒体和核基因组。线粒体疾病患者可在任何年龄发病，从新生儿期到成年后期不等，具有不同的器官受累和神经表现，包括神经发育迟缓、癫痫发作、类似中风的发作、运动障碍、视神经病变、肌病和神经病。直到最近，骨骼肌活检分析仍然是诊断算法的重点，但下一代测序技术和多组学分析的范围和可用性的显著进步，彻底改变了线粒体疾病的诊断。目前，大多数类型的线粒体疾病还没有特定的治疗方法，尽管该领域的临床试验研究正在兴起。在这种情况下，积极管理癫痫发作、类似中风的发作、肌张力障碍、脑干功能障碍和帕金森病，对于提高患者的生活质量和降低死亡率就显得更为重要。
