Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations
Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations
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DOI：
10.1136/jnnp.2009.176404
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发表时间：
2010-02-01
影响因子：
11
通讯作者：
Yan, Chuanzhu
中科院分区：
文献类型：
--
作者：
Wen, Bing;Dai, Tingjun;Yan, Chuanzhu
脂质沉积性肌病（LSM）是一组以骨骼肌为主要受累部位的异质性脂质代谢紊乱，其特征为肌纤维中甘油三酯的蓄积。在过去的15年中，中国文献报道了200多例LSM，但确切的致病机制仍不清楚。目的为了更深入地了解LSM的代谢和遗传功能障碍，作者描述了一组中国LSM患者，他们对单独核黄素治疗非常敏感方法1995-2007年在我们的神经肌肉实验室收集的19名连续的LSM患者，他们对核黄素有显著的反应，并表现为近端肌无力，结果19例患者均经肌肉病理学检查确诊为LSM。17例患者根据血酰基肉毒碱谱和尿有机酸分析怀疑患有多重酰基辅酶A脱氢酶缺乏症（MADD）。18例患者ETFDH基因共发现19个新突变，其中纯合子1例，复合杂合子16例，单一杂合子1例。ETFA和ETFB基因未发现致病性突变。Western blot分析显示，除1例患者外，其余患者的ETF：QO表达均无明显下降。结论研究结果提示，大多数中国RR-LSM患者是由ETFDH基因突变引起的伴有独特肌病的轻度MADD所致。
Background Lipid-storage myopathy (LSM), defined by triglyceride accumulation in muscle fibres, is a heterogeneous group of lipid metabolic disorders predominantly affecting skeletal muscle. In the past 15 years, more than 200 cases of LSM have been reported in the Chinese literature, but the accurate pathogenic mechanisms are still unknown.Objective In order to gain more insight into the metabolic and genetic dysfunctions of LSM, the authors described a group of Chinese patients with LSM who were very responsive to isolated riboflavin treatment ( riboflavin responsive LSM, RR-LSM).Methods Nineteen consecutive LSM patients collected during 1995-2007 in our Neuromuscular Laboratory who were dramatically responsive to riboflavin and presented with proximal muscle weakness, exercise intolerance and elevated serum CK but without episodic encephalopathy were subjected to pathological, biochemical and molecular analysis.Results On the basis of muscle pathology, all 19 patients were diagnosed as LSM. Seventeen patients were suspected of having multiple acyl-coenzyme A dehydrogenase deficiency ( MADD) according to blood acylcarnitine profiles and urine organic acid analysis. Genetic analysis identified 19 novel mutations in ETFDH gene in 18 patients, among which one was homozygote, 16 were compound heterozygotes, and one was a single heterozygote. No pathogenic mutation was detected in ETFA or ETFB genes. Western blot analysis showed there was no significant decrease in ETF:QO expression except for one patient.Conclusions The research findings suggest that the majority of Chinese patients with RR-LSM are caused by a mild type of MADD with unique myopathy which is due to ETFDH gene mutation.