The Clinical, Pathological, Biochemical And Genetic Research On A Genealogy Of Lipid Storage Myopathy

Objective:We summarize the clinical, pathological, biological features andgenetic characteristics of a lipid storage myopathy (LSM) genealogy inorder to clarify the causes and put forward specific prevention, treatment,and genetic counseling.Materials and Methods:We collected the clinical material of the proband and lineal relativesretrospectively. We detected the levels of serum acyl-carnitine whichcould predicted the subtle of LSM and the corresponding gene mutationthrough tandem mass spectrometry testing. Through the analysis ofsequencing the PCR amplification products, we examined the suspiciousmutations for further confirmation of the diagnosis.Results:1. Clinical characteristics:There was a relapse and remission process which has a subacuteonset of all patients. The most common clinical symptoms were muscleweakness and exercise intolerance. The proximal muscles, chewingmuscles, neck, trunk muscle were affected, accompanied by paresthesiaof peripheral nerve. Treatment with the combination of hormones, B vitamins, coenzyme Q10and ATP was effective. In addition, treatmentwith riboflavin solely was significantly effective.2. Pathological features:Muscle Biopsy study showed that there were increased lipiddroplets in muscle fibers. Furthermore, screen bubble or fissure in reddye could be seen in muscle fibers which were stained with oil red O.3. Biological features:The levels of serum acyl-carnitine mildly increased in3out of5patients, which supported that the disease was involved with the multipleacyl-CoA dehydrogenase deficiency (MADD).4. Genetic testing results:We identified a c.1669G>A(Glu557Lys) mutation in the ETFDHgene as a new missense mutation in the genetic analysis of Ⅰ1,c.770A>G(Tyr257Cys) and c.1669G>A(Glu557Lys) mutations in geneanalysis of Ⅱ3, Ⅱ4,Ⅱ5and Ⅲ2. These results further confirmed thatthere was multiple acyl-CoA dehydrogenase deficiency in thisgenealogy.Conclusions:In this study, we found that these patients were characterized bymuscle weakness involved with proximal limb muscle, chewing muscles,neck, trunk muscle. The pathological features of muscle biopsy study inthese patients were lipid deposition in muscle fibers. The levels of serum acyl-carnitine showed a positive correlation between MADD and thedisease. Genetic testing proved that this disease was caused by ETFDHgene mutations. In addition, a single riboflavin treatment is effective. Inconclusion, tandem mass spectrometry testing in blood is helpful forprimary screening of LSM subtypes, which provides a certain directionfor genetic testing.