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.

Clinical and laboratory investigation were performed. Detailed analysis of muscle biopsy specimen included enzyme histochemistry, electron microscopy, quantitative proteomics, immunofluorescence of the respiratory chain subunits, western blot and genetic analyses.

The patients showed an acylcarnitine profile in blood suggestive of multiple acyl-coenzyme A dehydrogenase deficiency (MADD), but no genetic explanation was found by whole genome or exome sequencing. The investigations also showed that muscle tissue in this group of patients exhibit a characteristic morphological and proteomic profile. 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. 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 a novel important differential diagnosis with characteristic features.