Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
J Neuromuscul Dis. 2021;8(3):401-417. doi: 10.3233/JND-200621.
Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking.
The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the "treatabolome" project.
A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect.
Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively.
This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.
代谢性肌病是一组异质性肌肉疾病，通常以运动不耐受、肌痛和进行性肌无力为特征。一些此类疾病已有有效治疗方法，但尽管我们对与糖原储存、脂质代谢和β氧化相关的代谢性肌病的发病机制已有充分了解，但将治疗与确切的致病遗传缺陷联系起来的证据尚缺乏。
本研究旨在整理所有已发表的关于上述代谢性肌病药物治疗的证据，并将其与遗传突变联系起来，以便以可用于数据库的格式进行进一步计算，这符合“治疗组学”项目的原则。
系统检索了所有关于药物治疗糖原储存和脂质代谢相关代谢性肌病的疗效的证据，纳入标准是治疗患者的遗传变异可用，以便将治疗结果与遗传缺陷联系起来。
最初确定的 1085 篇文章中，有 268 篇全文文章进行了资格评估，其中 87 篇文章进入了最终的数据提取。研究最多的代谢性肌病是庞贝病（45 篇文章）、与 ETFDH 基因突变相关的多种酰基辅酶 A 脱氢酶缺乏症（15 篇文章）和系统性原发性肉碱缺乏症（8 篇文章）。这些疾病最常见的治疗管理策略分别是酶替代疗法、核黄素和肉碱补充。
本系统综述以可计算的格式提供了与治疗代谢性肌病相关的遗传缺陷的治疗证据，适合在 treatabolome 系统中进行数据库管理，这将使临床医生在诊断时能够为其患者获得适当治疗选择的证据。
