A Novel Mutation In PNPLA2 Causes Neutral Lipid Storage Disease With Myopathy:A Case Report And Literature Review

Background and purpose:Neutral lipid storage disease with myopathy?NLSDM?,a rare lipid deposition myopathy with an autosomal recessive inheritance pattern,arises from mutations in the patatin-like phospholipase domain containing 2?PNPLA2?gene that encodes an adipose triglyceride lipase?ATGL?.Pathogenic mutations cause abnormal deposition of triglycerides in skeletal muscle,myocardium,liver and peripheral blood granulocytes,which can cause multiple systemic damage in clinical practice and have various manifestations,which are easy to be misdiagnosed and missed.In this study,the clinical features,muscle pathology,PNPLA2 gene mutation characteristics of a newly mutated case of PNPLA2 gene were analyzed,and relevant literature was reviewed to improve clinical diagnose of NLSDM.Methods:?1?The clinical features,auxiliary examination,muscle pathology and mutation characteristics of PNPLA2 gene in a newly diagnosed case of NLSDM caused by novel PNPLA2 gene mutation in our hospital were retrospectively analyzed.?2?To review the NLSDM cases with relatively complete case data between the time January 2007 to March 2019 through searching the CNKI,Wanfang,Medline and Pubmed datebase with these key words: Lipid storage myopathy,neutral lipid storage disease,neutral Lipid storage disease with myopathy,rimmed vacuoles,PNPLA2 gene.Results:?1?This patient was a 33-year-old han Chinese woman with the main clinical manifestations of limb muscle weakness and muscular atrophy,especially on the right side.Creatine kinase?CK?was mildly to moderately elevated.Serum triglyceride levels were normal.Electromyography showed myopathic changes.In the peripheral blood smears,numerous fat droplets were observed in the leukocytes by ORO staining.Muscle biopsy revealed large amounts of lipid droplets and plenty of rimmed vacuoles?RV?in the fibers.Targeted capture and next generation sequencing revealed novel PNPLA2 gene homozygous frameshift mutation,c.750₇57del?p.Q250fs?.?2?A total of 50 cases of NLSDM were retrieved from domestic and foreign databases,including 28 males and 22 females,with an average age of 32.0�12.7years old,time from onset to diagnosis was 8.6�6.7 years.Most of the cases were mainly manifested by limb muscle weakness,and 2 of them were manifested as asymptomatic hyperCKemia.54% presented asymmetric limb muscle weakness?96%obvious on the right side,4% obvious on the left side?,68% proximal weakness,23%distal weakness,and 9% shows no difference in the degree of involvement between the distal and proximal limbs.The serum CK level was1394�909 U/L,and the serum triglyceride level of 22% patients was higher than normal.The Jordans bodies were found in all patients with the peripheral blood smears ORO staining.The major changes in muscle pathology were lipid accumulation?98%?and RV?27%?,and all the 13 patients with RV were of Asian population.Lipid droplet deposition was found in 5 cases of skin biopsy.PNPLA2 gene mutation detection revealed that 76% were homozygous mutations,24% were complex heterozygous mutations,and missense mutations?57%?and deletion mutations?20%?were found in a large number of mutation types.In patients with multisystem involvement,Cardiomyopathy?42%?,liver damage?19%?,neurologic deafness?15%?,pancreatitis?6%?,diabetes?8%?,hypothyroidism?4%?and cognitive impairment?2%?.Conclusion:1.The main clinical manifestation of NLSDM is the asymmetrical limb weakness that occurs in young and middle-aged people.The right limb is more severe and more common.This disease can involve multiple systems.2.The main changes of muscle pathology were lipid accumulation,some of which were associated with RV which was a trend in Asian patients.ORO staining of peripheral blood smear and serum creatine kinase and triglyceride detection can assist diagnosis.3.The diagnosis of NLSDM is based on the mutation detection of the pathogenic gene PNPLA2,and the mutation types are mostly homozygous missense mutations.This patient is a homozygous frameshift mutation at the locus of PNPLA2 gene c.750₇57del?p.Q250fs?,which is a newly reported mutation for the first time.