Lipid storage myopathies are considered inborn errors of metabolism affecting the fatty acid metabolism and leading to accumulation of lipid droplets in the cytoplasm of muscle fibers. Specific diagnosis is based on investigation of organic aids in urine, acylcarnitines in blood and genetic testing. An acquired lipid storage myopathy in patients treated with the antidepressant drug sertraline, a serotonin reuptake inhibitor, has recently emerged as a new tentative differential diagnosis. We analyzed the muscle biopsy tissue in a group of 11 adult patients with muscle weakness and lipid storage myopathy which developed at a time when they were on sertraline treatment. This group comprise most patients with lipid storage myopathies in western Sweden during the recent nine-year period. By enzyme histochemistry, electron microscopy, quantitative proteomics, immunofluorescence of the respiratory chain subunits, western blot and genetic analyses we demonstrate that muscle tissue in this group of patients exhibit a characteristic morphological and proteomic profile. The patients also showed an acylcarnitine profile in blood suggestive of multiple acyl-coenzyme A dehydrogenase deficiency, but no genetic explanation was found by whole genome or exome sequencing. By proteomic analysis the muscle tissue revealed a profound loss of Complex I subunits from the respiratory chain and to some extent also deficiency of Complex II and IV. Most other components of the respiratory chain as well as the fatty acid oxidation and citric acid cycle were upregulated in accordance with the massive mitochondrial proliferation. The respiratory chain deficiency was verified by immunofluorescence analysis, western blot analysis and enzyme histochemistry. The typical ultrastructural changes of the mitochondria included pleomorphism, dark matrix and frequent round osmiophilic inclusions. Our results show that lipid storage myopathy associated with sertraline treatment is a mitochondrial disorder with respiratory chain deficiency and is an important differential diagnosis with characteristic features.

脂质储存肌病被认为是先天性代谢缺陷，影响脂肪酸代谢并导致脂滴在肌肉纤维细胞质中积累。特异性诊断基于对尿液中有机辅助物、血液中酰基肉碱和基因检测的调查。接受抗抑郁药物舍曲林（一种 5-羟色胺再摄取抑制剂）治疗的患者的获得性脂质贮积肌病最近已成为一种新的初步鉴别诊断。我们分析了一组 11 名患有肌肉无力和脂质储存肌病的成年患者的肌肉活检组织，这些患者在接受舍曲林治疗时出现。该群体包括最近 9 年瑞典西部的大多数脂质贮积肌病患者。通过酶组织化学、电子显微镜、定量蛋白质组学、呼吸链亚基的免疫荧光、蛋白质印迹和遗传分析，我们证明这组患者的肌肉组织表现出特征性的形态学和蛋白质组学特征。患者还在血液中显示酰基肉碱谱，提示多种酰基辅酶 A 脱氢酶缺乏症，但通过全基因组或外显子组测序未发现遗传解释。通过蛋白质组学分析，肌肉组织显示复合物 I 亚基从呼吸链中严重丢失，并且在某种程度上也缺乏复合物 II 和 IV。呼吸链的大多数其他成分以及脂肪酸氧化和柠檬酸循环根据线粒体的大量增殖上调。通过免疫荧光分析、western blot 分析和酶组织化学验证呼吸链缺陷。 线粒体的典型超微结构变化包括多形性、深色基质和频繁的圆形嗜渗性包涵体。我们的结果表明，与舍曲林治疗相关的脂质储存肌病是一种伴有呼吸链缺陷的线粒体疾病，是一种具有特征性特征的重要鉴别诊断。