The Clinical Features And Gene Mutation Characteristics Of The Electron Transfer Flavoprotein Dehydrogenase In Riboflavin Responsive Lipid Storage Myopathy In Jiangxi Province

Objectives：Riboflavin responsive lipid storage myopathy(RR-LSM) mostly belongs tomultiple acyl-CoA dehydrogenation deficiency type III, which electron transferringflavoprotein dehydrogenase (ETFDH) gene mutations are the major cause.Theclinical features of RR-LSM include fluctuating weekness of proximal extremitiesand exercise intolerance. The first case of RR-LSM was reported in1976and inChina was1995. To date, more than100cases has been reported which distribute inShangdon,Beijing,Taiwan,Hongkong,Shanghai,Fujian.The study of ETFDH genesmutations found that there were hot spot mutations in area of China: c.250G>A inSouthern China, c.770A>G and c.1227A>C in Northern China respectively. It isunclear whether patients in Jiangxi have above-mentioned hot spot mutations and theclinical features follow the general rule.Herein,we study the clinical manifestationsand the features of ETFDH gene mutations in10patients with RR-LSM.Material and methods：The clinical data of10cases in the First Affiliated Hospital of NanchangUniversity from September2011to March2013with lipid storage myopathyconfirmed by muscle biopsy who were dramatically responsive to riboflavin werecollected. They were from Jiangxi province.Patients with LSM caused by othercauses were excluded. Analysis of ETFDH genes was performed in10patients and100healthy controls.Results:The percentage of RR-MADD is7.14%(10/140) during the period of musclebiopsy. Nine patients were sporadic while one had positive family history.Theaverage age at onset was39.1±8.84years.The major symptoms were exerciseintolerance (100%),muscle weakness(100%), myalgia(30%), musclesoreness(30%),hypoesthesia(20%).The most involvement of muscle weakness wereproximal lower limb(100%), distal lower limb(40%), neck(40%), masseter(40%),proximal upper limb(30%).One patient vomited obviously after fat food.Before onset,three patients had diarrhea,pregnancy and exercise.The elevation of CK rangedfrom346to8298(normal reference0-171U/L) and one patient’s CK was normal.Many fibers were filled with amount of lipid droplets in all patients, predominantly intype I fibers. All patients had ETFDH genes mutations.5were compoundheterozygous mutations while the other5were single heterozygous mutation.Wefound14mutations,containing11missense mutations (including1mutation at thestart codon),2nonsense mutions and1deletion mutation,in which9were reportedmutations(c.1395T>G、 c.l1773-1774del、 c.1084G>A、 c.3G>C、 c.389A>T、c.1227A>C、 c.1211T>C、 c.770A>G、 c.1399G>)and5were novel mutations（c.303T>A、c.518T>G、c.1810G>T、c.295C>T、 c.1586A>G）.Conclusions:The clinical features of RR-LSM are muscle weakness in proximal lowerlimb,neck and masseter, exercise intolerance, myalgia and muscle soreness with orwithout slight extramuscle manifestation.ETFDH mutations are the major cause ofRR-LSM.The spectrum of ETFDH mutations is heterogeneity in Jiangxiprovince.There are many new mutations. Mutation hotspot and the mutation hotspotsin China were not found in our study..