The Clinical Characteristics And Gene Mutation Analysis Of ETFA,ETFB, ETFDH In Han Patient Diagnosed As Lipid Storage Myopathy In Jiangxi Province

Objective:To investigate the clinical characteristics and gene mutation analysis of ETFA、ETFB、ETFDH in Han patient diagnosed as lipid storage myopathy in jiangxi province.Methods : We retrospectively analyzed the clinical manifestation,auxiliary examination and the treatment effect in 38 cases of LSM patients diagnosed by muscle biopsy in our department over last 15 years;by the analysis of the follow-up,we studied the prognosis and recurrence after initial therapy in some LSM patients;through the analysis of the genetic testing,we concluded the characteristics of the ETFA、ETFB、ETFDH gene mutations.Results:(1)The main clinical symptoms of LSM patients in jiangxi province include proximal weakness(100%), exercise intolerance(100%); some LSM patients’ cervical extensor muscles(42.11%)and masticatory muscles(23.68%)were significantly affected,and muscle soreness(23.68%),numbness(15.79%)sometimes happened; few LSM patients’ throat muscle(2.63%)and respiratory muscles(7.89%)were involved.LSM was easily misdiagnosed as multiple myositis(23.68%), chronic hepatitis(5.26%)and myocarditis(5.62%).( 2)Serum creatine enzymes(CK)increased(228.4-14927.0 IU/L)(normal range 38.0-174.0 IU/L)before treatment and decreased significantly(P<0.05)after treatment in this group of patients,and the CK level before treatment was negatively related to the degree of iliopsoas muscle weakness(P<0.001).(3)Electromyogram showed muscle damage in 55.26%of all and 15.79% of them showed ne-uropathy and 28.95% of them showed normal.Electromyography chan-ges were obvi-ously related to the level of CK and CK levels of muscle damage group was obviously h igher than that of neurogenic damage group and normal group(P<0.001).(4) A lot of cri-briform vacuoles Showing in HE-staining is the major feature of muscular pathology in t he LSM patients,and oil red O staining showed a large number of lipid droplets filled in.A lot of necrotic fibers can be seen in 6 cases among them.The positive rate of myogenic abnormality showed in EMG in the patients with large numbers of necrotic fibers showed in HE was significantly higher than that the patients without large Numbers of necrotic fibers(P<0.05).(5)Cortisol alone was used as a first line of treatmen after the diagnosis of LSM in 3 cases,l-carnitine alone in 1 case,Vit B2 alone in 10 cases,combined treatm-ent in 24 cases,and curative effect were significantly.32 cases were followed up after init-ialtreatment.3 cases were followed up for more than 10 years;11 cases were followed up from 5 to 10 years;14 cases were followed up from 1 to 5 years;4 cases were followed up for less than 1 years.Daily life and work of 14 LSM patients followed up were normal and 3 cases showed poor exercise tolerance.Of 15 cases(46.88%)with recurrence after initial treatment,6 cases had 1 outbreak,5 cases had 2 outbreaks,4 cases had 3 outbre-aks.Patients had stopped taking drugs before relapse;the possible causal factors included vigorous exercise(4 case times),upper respiratory tract infection(1 case times),no clear trigger(23 case times).All patients were recovered after next treatment.(6) Of 10 patients who had ETFA、ETFB 、ETFDH genes mutation detection,all the patients had no disease-causing ETFA、ETFB genes mutations,9 patients had disease-causing ETFDH genes mutation, 1 patients had no disease-causing ETFDH genes mutation.4 were compound heterozygous mutations,5 were single heterozygous mutation,and the other 1was Homozygous mutations.We found 11 mutations,containing 10 missense mutations,1deletion mutation,in which 9 were reported mutations and 2 were novel mutations.Among them,one Hot spot mutation existed(c.1211T>C,Frequency of 2times).Conclusion:(1)The main clinical symptoms of LSM patients in jiangxi province include proximal weakness(100%), exercise intolerance(100%); some LSM patients’ cervical extensor muscles(42.11%)and masticatory muscles(26.32%)were significantly affected.(2)The values of creatine kinase in all the cases were increased to different degree.CK level may be as a parameter in evaluating the severity and prognosis of disease.(3)EMG showed myogenic abnormality in part of LSM patients, and myogenic abnormality showed in electromyography was obviously related to the lev-el of CK and the degree of necrotic fibers showed in HE.(4)most patients have a good prognosis.the possible causal factors included stopping medication,vigorous exercise,upper respiratory tract infection, etc.(5)ETFDH mutations are the major cause of RR-LSM.The spectrum of ETFDH mutations is heterogeneity in Jiangxi province.The c.1211T>C gene mutation may be the Hot spot mutation in Jiangxi province.