Debray François-Guillaume, Lambert Marie, Mitchell Grant A
Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine, University of Montreal, Sainte-Catherine, Montreal, Quebec, Canada.
Curr Opin Pediatr. 2008 Aug;20(4):471-82. doi: 10.1097/MOP.0b013e328306ebb6.
Mitochondrial diseases are a major category of childhood illness that produce a wide variety of symptoms and multisystemic disorders. This review highlights recent clinically important developments in diagnostic evaluation and treatment of mitochondrial diseases.
Major advances have been made in understanding the genetic bases of mitochondrial diseases. Molecular defects have recently been reported in mitochondrial DNA maintenance, RNA translation and protein import and in mitochondrial fusion and fission, opening new areas of cell disorder. Diagnostic testing is struggling to keep pace with these fundamental discoveries. The diagnostic approach to children suspected of mitochondrial disease is rapidly evolving but few patients have a molecular diagnosis. A better notion of the prognosis of affected children is emerging from studies of long-term outcome. Some therapeutic successes are reported, such as in coenzyme Q deficiency conditions.
Mitochondrial diseases can present with signs in almost any organ. Well planned clinical evaluation is the key to successful diagnostic work-up of mitochondrial diseases. An approach is presented for further testing in specialized laboratories. Mitochondrial diseases can be caused by mutations in mitochondrial DNA or, more commonly in children, in nuclear genes. Mitochondrial DNA mutations pose special challenges for genetic counseling and prenatal diagnosis. Supportive treatment and avoidance of environmental stresses are important aspects of patient care. Specific treatment of mitochondrial diseases is in its infancy and is a major challenge for pediatric medicine.
线粒体疾病是儿童疾病的主要类型，可产生各种各样的症状和多系统紊乱。本综述重点介绍线粒体疾病诊断评估和治疗方面近期具有临床重要意义的进展。
在理解线粒体疾病的遗传基础方面取得了重大进展。最近在线粒体DNA维持、RNA翻译、蛋白质导入以及线粒体融合和裂变方面报道了分子缺陷，开辟了细胞紊乱的新领域。诊断检测难以跟上这些基础发现的步伐。对疑似线粒体疾病儿童的诊断方法正在迅速演变，但很少有患者获得分子诊断。对受影响儿童预后的更好认识正从长期结局研究中显现出来。报告了一些治疗成功案例，如在辅酶Q缺乏症病例中。
线粒体疾病几乎可在任何器官出现体征。精心规划的临床评估是线粒体疾病成功诊断检查的关键。本文介绍了在专业实验室进行进一步检测的方法。线粒体疾病可由线粒体DNA突变引起，在儿童中更常见的是由核基因中的突变引起。线粒体DNA突变给遗传咨询和产前诊断带来特殊挑战。支持性治疗和避免环境压力是患者护理的重要方面。线粒体疾病的特异性治疗尚处于起步阶段，是儿科学面临的一项重大挑战。
