Clinical Study And Genetic Research On Lipid Storage Myopathy

Lipid storage myopathy is fatty acid oxidation defects resulting in muscle excessive lipid storage caused by multiple reasons.In 1969,Bradley first used the term 'lipid storage myopathy' to describe a young patient with proximal myopathy and excessive lipid accumulation in typeâ… muscle fibres.Now,the numbers of the cases diagnosed of lipid storage myopathy by muscle biopsy are growing up more and more,etiological diagnosis is becoming more important than before.Organic acids because of fatty acid oxidation defects are produced and come into urine.The level of fatty acid in blood increaded in some disorders of fatty acid oxidation defects,and urine organic acids and plasma acylcarnitine increase in some disorders.Some patients of multiple acyl-CoA dehydrogenation deficiency(MADD)often respond to pharmacological doses of riboflavin and this kind of disease is called by riboflavin-responsive MADD.ETFDH mutations may be associated with riboflavin-responsive MADD.According to above information,the research is consised of three parts as following.PART ONE:Clinical study on lipid storage myopathy easily misdiagnosedObjective:To analyze the clinical and pathological features of lipid storage myopathy(LSM).Methods:The clinical datas of 25 cases of LSM were collected and analyzed retorspectively to find charactetistic changes.Results: The clinical features of the 25 patients were chronic onset or subacute onset, proximal muscle weakness and exercise intolerance.Cold and exertion are common inducement.Frozen sections of muscle biopsy samples showed many fibers contained numerous vacuoles which was stained by Oil Red O.Conclusion: Etiological diagnosis of LSM cannot be made according to the clinical symptom and signs.PART TWO:The possible reasons of lipid storage myopathy throuth screening urine organic acids and plasma acylcarnitineObjective:To study the possible reasons of lipid storage myopathy throuth screening urine organic acids and plasma acylcarnitine.Methods:To screen urine organic acids and plasma acylcarnitine of 9 cases of lipid storage myopathy,and riboflavin treatment was used for possible MADD.Results:Possible diagnosis of MADD is made in 8 cases of 9 cases of lipid storage myopathy and the patients of possible MADD improved within days of starting riboflavin.Conclusion:The screens of urine organic acids and plasma acylcamitine are useful tool to diagnose MADD.PART THREE:Genetic research of ETFDH gene mutations on riboflavin-responsive MADDObjective:To identify correlativity between ETFDH mutation and riboflavinresponsive MADD.Methods:Genomic DNA-based PCR amplifications and sequence analysis of the total 13 exons of the human ETFDH gene were carried out for 4 cases of possible MADD according to screening urine organic acids.Results:All 4 patients were demonstrated to have mutations in the ETFDH gene.Conclusion:The mutations of ETFDH gene may be responsible for riboflavin- responsive MADD.Total conclusion:1.Etiological diagnosis cannot be made according to the clinical symptom and sign of LSM.2.The screen of urine organic acids and plasma acylcarnitine are useful tool to diagnose possible MADD.3.The mutations of ETFDH gene may be responsible for riboflavinriboflavin-responsive MADD.4.Clinical improvement has been made after riboflavin treatment in some of MADD..