脂肪沉积性肌病

Lipid storage myopathy

脂肪沉积性肌病(LSM)是一组以脂肪在肌纤维内异常聚集为主要肌肉病理改变的病因异质性疾病。LSM在中国人群中相对常见,经肌肉活体组织检查(活检)证实的脂质沉积下肌病占肌肉活检总数的3%~5%。LSM的病理机制是肌肉组织内脂肪酸氧化代谢障碍。中国人的LSM主要由晚发型多酰基脂酰辅酶A脱氢缺陷(MADD)引起,其分子病理缺陷是电子转运黄素蛋白脱氢酶基因突变。ETFDH c.250G>A是中国南方最为常见的突变,c.770A>G和c.1227A>C在北方和南方均常见。几乎所有的晚发型MADD对核黄素治疗均有明显疗效。在中国,LSM的第二个较为常见的病因是中性脂肪沉积病伴肌病,由编码甘油三酯脂酶的PNPLA2基因突变导致。远端肌群受累和不对称的肌萎缩、肌无力可能提示本病的诊断。少数肉碱转运障碍和其他酰基肉碱脱氢酶缺陷的患者也有可能表现为LSM。某些类型的线粒体病,如线粒体DNA缺失综合征和线粒体脑肌病伴乳酸血症和卒中样发作综合征可能有继发的肌纤维内脂肪聚集。一些皮肌炎和接受激素治疗的患者,肌肉活检可见不同程度的脂肪增多。

Lipid storage myopathy (LSM) is an etiologically heterogeneous group of lipid metabolic disorders characterized by accumulation of light microscopic lipid droplets in muscle fibers. This disease seems to be more common in Chinese population accounting for 3%-5% of total muscle biopsies in several large neuromuscular centers in China. The pathogenesis of LSM is the impairment of fatty acid oxidation in muscle fibers. Late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD) caused by electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation has been demonstrated to be the main molecular defect in China. Three frequent ETFDH mutations were identified: c.250G>A in patients from South China, and c.770A>G and c.1227A>C in those from both South and North China. More importantly, almost all late-onset MADD are dramatically responsive to riboflavin supplementation. Neutral lipid storage disease with myopathy (NLSDM) caused by mutations in PNPLA2 gene is the second common cause of Chinese LSM.Distal muscle involvement and asymmetrical muscle weakness and atrophy are common in primary symptoms of NLSDM which may be the first clue indicating the diagnosis of NLSDM.There were also a few case reports showing that LSM may be caused by carnitine transport defect and other deficiencies of acyl-coenzyme A dehydrogenase involved in fatty acid beta oxidation. Increased lipid droplets accumulation in muscle fibers may also be a secondary consequence of mitochondrial myopathy (mtDNA depletion syndrome or MELAS), dermatomyositis and steroid treatment.