Ørngreen Mette Cathrine, Vissing John
Copenhagen Neuromuscular Centre, University of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Curr Treat Options Neurol. 2017 Sep 21;19(11):37. doi: 10.1007/s11940-017-0473-2.
Metabolic myopathies are disorders affecting utilization of carbohydrates or fat in the skeletal muscle. Adult patients with metabolic myopathies typically present with exercise-induced pain, contractures or stiffness, fatigue, and myoglobinuria. Symptoms are related to energy failure. Purpose of review In this review, the current treatment options, including exercise therapy, dietary treatment, pharmacological supplementation, gene transcription, and enzyme replacement therapy, are described. Recent findings Recognition of the metabolic block in the metabolic myopathies has started the development of new therapeutic options. Enzyme replacement therapy with rGAA has revolutionized treatment of early onset Pompe disease. Supplements of riboflavin, carnitine, and sucrose show promise in patients with respectively riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, primary carnitine deficiency, and McArdle disease. Treatment with citric acid cycle intermediates supply by triheptanoin seems promising in patients with glucogenoses, and studies are ongoing in patients with McArdle disease. Summary Treatment of metabolic myopathies primarily relies on avoiding precipitating factors and dietary supplements that bypass the metabolic block. Only a few of the used supplements are validated, and further studies are needed to define efficacious treatments. Further potential treatment targets are molecular therapies aimed at enzyme correction, such as chaperone therapy, gene therapy, gene expression therapy, and enzyme replacement therapies.
代谢性肌病是影响骨骼肌碳水化合物或脂肪利用的疾病。成年代谢性肌病患者通常表现为运动诱发的疼痛、挛缩或僵硬、疲劳和肌红蛋白尿。症状与能量衰竭有关。综述目的 在本综述中,描述了当前的治疗选择,包括运动疗法、饮食治疗、药物补充、基因转录和酶替代疗法。最新发现 对代谢性肌病中代谢障碍的认识开启了新治疗选择的研发。用重组人酸性α-葡萄糖苷酶进行酶替代疗法彻底改变了早发型庞贝病的治疗。核黄素、肉碱和蔗糖补充剂分别在核黄素反应性多种酰基辅酶A脱氢酶缺乏症、原发性肉碱缺乏症和麦克尔憩室病患者中显示出前景。用三庚酸甘油酯提供柠檬酸循环中间体进行治疗在糖原贮积病患者中似乎有前景,并且正在对麦克尔憩室病患者进行研究。总结 代谢性肌病的治疗主要依赖于避免诱发因素和绕过代谢障碍的饮食补充剂。只有少数使用的补充剂得到了验证,需要进一步研究来确定有效的治疗方法。进一步的潜在治疗靶点是旨在酶校正的分子疗法,如伴侣疗法、基因疗法、基因表达疗法和酶替代疗法。