Magner Martin, Kolářová Hana, Honzik Tomáš, Švandová Ivana, Zeman Jiří
Department of Paediatrics and Adolescent Medicine, Ke Karlovu 2, 128 08 Praha 2, Czech Republic, tel. +420-224967733, fax +420-224967113, e-mail: jzem @lf1.cuni.cz.
Dev Period Med. 2015 Oct-Dec;19(4):441-9.
Mitochondrial disorders (MD) represent a clinically, biochemically and genetically heterogeneous group of diseases associated with dysfunction of the oxidative phosphorylation system and pyruvate dehydrogenase complex. Our aim was to illustrate the most common clinical presentation of MD on the example of selected diseases and syndromes. The minimal prevalence of MD is estimated as 1 to 5,000. MD may manifest at any age since birth until late-adulthood with acute manifestation or as a chronic progressive disease. Virtually any organ may be impaired, but the organs with the highest energetic demands are most frequently involved, including brain, muscle, heart and liver. Some MD may manifest as a characteristic cluster of clinical features (e.g. MELAS syndrome, Kearns-Sayre syndrome). Diagnostics includes detailed history, the comprehensive clinical examination, results of specialized examinations (especially cardiology, visual fundus examination, brain imaging, EMG), laboratory testing of body fluids (lactate, aminoacids, organic acids), and analysis of bioptic samples of muscle, skin, and liver, eventually. Normal lactate level in blood does not exclude the possibility of MD. Although the aimed molecular genetic analyses may be indicated in some of mitochondrial diseases, the methods of next generation sequencing come into focus. Examples of treatment are arginine supplementation in MELAS syndrome, ketogenic diet in pyruvate oxidation disorders or quinone analogs in patients with LHON. Conclusion: The clinical suspicion of a mitochondrial disorder is often delayed, or the disease remains undiagnosed. The correct diagnosis and adequate treatment can improve prognosis of the patient. Access to genetic counseling is also of great importance.
线粒体疾病(MD)是一组在临床、生化和遗传方面具有异质性的疾病,与氧化磷酸化系统和丙酮酸脱氢酶复合体功能障碍相关。我们的目的是以选定的疾病和综合征为例,阐述MD最常见的临床表现。MD的最低患病率估计为1/5000至1/1000。MD可在从出生到成年晚期的任何年龄出现,表现为急性发作或慢性进行性疾病。实际上,任何器官都可能受损,但能量需求最高的器官最常受累,包括脑、肌肉、心脏和肝脏。一些MD可能表现为特征性的临床特征群(如MELAS综合征、凯-赛综合征)。诊断包括详细的病史、全面的临床检查、专科检查结果(尤其是心脏病学、眼底检查、脑成像、肌电图)、体液实验室检测(乳酸、氨基酸、有机酸),最终还包括对肌肉、皮肤和肝脏活检样本的分析。血液中乳酸水平正常并不能排除MD的可能性。尽管在某些线粒体疾病中可能需要进行靶向分子遗传学分析,但新一代测序方法备受关注。治疗示例包括MELAS综合征补充精氨酸、丙酮酸氧化障碍采用生酮饮食或LHON患者使用醌类似物。结论:对线粒体疾病的临床怀疑往往延迟,或者疾病仍未得到诊断。正确的诊断和适当的治疗可以改善患者的预后。获得遗传咨询也非常重要。