@#To investigate the clinical，pathological and ETFDH gene mutation characteristics of riboflavinresponsive lipid storage myopathy（RRLSM） caused by ETFDH gene mutation.Methods The clinical and pathological data of 18 RR-LSM patients who were admitted to our hospital from January 2009 to December 2020 and confirmed by muscle biopsy pathology and gene testing were retrospectively analyzed. The Illumina NovaSeq highthroughput sequencing of peripheral blood DNA was performed for data reading and bioinformatics analysis.Results Among the 18 patients，there were 9 males and 9 females. The age of onset ranged from 9 to 60 years old（mean 29.83±13.44 years）. The course of disease ranged from 1 month to 22 years（mean 4.5 years）. The main clinical manifestations were proximal limb weakness and movement intolerance，accompanied by cervical extensor weakness in 14 cases，masticatory muscle weakness in 9 cases，dysphagia in 5 cases，nausea and poor appetite in 5 cases，and muscle pain and dyspnea in a few patients. Muscle pathology showed a large amount of lipid deposition in muscle fibers and a small amount of muscle fiber necrosis in 5 cases. Immunohistochemical staining indicated that the necrotic muscle fibers were mainly infiltrated by CD68（+） lymphophagocytes. All 18 patients were treated with riboflavin and had good efficacy. ETFDH gene mutation was detected in all cases in this study，including 15 cases（83.3%） with complex heterozygous mutation，2 cases（11.1%） with single heterozygous mutation，and 1 case（5.6%） with homozygous mutation. A total of 20 mutation sites were found，among which the most frequent mutation site was c.770A>G，accounting for 19.4%（7/36） of the allele，followed by c.1454C>G，accounting for 8.3%（3/36） of the allele. Conclusion RRLSM patients caused by ETFDH gene mutation are characterized by trunk axial muscle and masticatory muscle involvement. Muscle pathology found that there are a large number of lipid deposits in muscle fibers is an important basis for diagnosis. c.770A>G and c.1454C>G are the most common mutation sites of ETFDH gene in this grou.