Background:Very long chain acyl-CoA dehydrogenase deficiency(VLCADD)is an inherited metabolic disease caused by deleterious mutations in the ACADVL gene that encodes very long chain acyl-CoA dehydrogenase(VLCAD),and w...Background:Very long chain acyl-CoA dehydrogenase deficiency(VLCADD)is an inherited metabolic disease caused by deleterious mutations in the ACADVL gene that encodes very long chain acyl-CoA dehydrogenase(VLCAD),and which can present as cardiomyopathy in neonates,as hypoketotic hypoglycemia in infancy,and as myopathy in late-onset patients.Although many ACADVL mutations have been described,no prevalent mutations in the ACADVL gene have been associated with VLCADD.Herein,we report the clinical course of the disease and explore the genetic mutation spectrum in seven Chinese patients with VLCADD.Methods:Seven Chinese patients,from newborn to 17 years old,were included in this study.Tandem mass spectrometry was performed to screen for VLCAD defi ciency.All exons and fl anking introns of the ACADVL gene were analyzed using polymerase chain reaction and direct sequencing.Online analysis tools were used to predict the impact of novel mutations.Results:All cases had elevated serum levels of tetradecanoylcarnitine(C14:1)which is the characteristic biomarker for VLCADD.The phenotype of VLCADD is heterogeneous.Two patients were hospitalized for hypoactivity and hypoglycemia shortly after birth.Three patients showed hepatomegaly and hypoglycemia in infancy.The other two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis.Three of the patients died at the age of 6-8 months.Eleven different mutations in the ACADVL gene in the 7 patients were identified,including seven reported mutations(p.S22X,p.W427X,p.A213T,p.G222R,p.R450H,c.296-297delCA,c.1605+1G>T)and four novel mutations(p.S72F,p.Q100X,p.M437T,p.D466Y).The p.R450H and p.D466Y(14.28%,2/14 alleles)mutations were identifi ed in two alleles respectively.Conclusions:The clinical manifestations were heterogeneous and ACADVL gene mutations were heterozygous in the seven VLCADD Chinese patients.R450H may be a relatively common mutation in Asian populations.The genotype and phenotype had a certain correlation in our patients.展开更多
目的探讨4例极长链酰基辅酶A脱氢酶(very long chain acyl-coenzyme A dehydrogenase,VLCAD)缺乏症的临床特征及基因变异特点。方法对新生儿筛查中十四烯酰基肉碱(C14:1)≥0.4μmol/L的新生儿召回复查,通过串联质谱、基因检测确诊4例VL...目的探讨4例极长链酰基辅酶A脱氢酶(very long chain acyl-coenzyme A dehydrogenase,VLCAD)缺乏症的临床特征及基因变异特点。方法对新生儿筛查中十四烯酰基肉碱(C14:1)≥0.4μmol/L的新生儿召回复查,通过串联质谱、基因检测确诊4例VLCAD缺乏症患儿,对确诊患儿进行临床和基因变异分析。结果4例患儿血串联质谱结果中C14:1均特异性升高且首次召回复查值均低于初筛值,2例下降到正常范围,1例下降后仍>1μmol/L,1例仅轻微下降。4例患儿中共检出8种变异,以错义变异为主(5/8),并发现3种未报道过的新变异(p.Met344Val,p.Ala416Val,c.1077+6T>A)。均无明显异常临床表现。结论本研究结果扩宽了VLCAD缺乏症的基因谱,为临床VLCAD缺乏症的筛查和诊断提供了经验,为产前诊断提供了依据。展开更多
基金supported by grants from the National Natural Science Foundation of China(81170811,30973216)Shanghai School Board(12ZZ114)and Shanghai Health Bureau(20134005)+1 种基金supported by grants from the Major Program of Shanghai Committee of Science and Technology(11dz195030)the National Key Technology R&D Program(2012BAI09B04).
文摘Background:Very long chain acyl-CoA dehydrogenase deficiency(VLCADD)is an inherited metabolic disease caused by deleterious mutations in the ACADVL gene that encodes very long chain acyl-CoA dehydrogenase(VLCAD),and which can present as cardiomyopathy in neonates,as hypoketotic hypoglycemia in infancy,and as myopathy in late-onset patients.Although many ACADVL mutations have been described,no prevalent mutations in the ACADVL gene have been associated with VLCADD.Herein,we report the clinical course of the disease and explore the genetic mutation spectrum in seven Chinese patients with VLCADD.Methods:Seven Chinese patients,from newborn to 17 years old,were included in this study.Tandem mass spectrometry was performed to screen for VLCAD defi ciency.All exons and fl anking introns of the ACADVL gene were analyzed using polymerase chain reaction and direct sequencing.Online analysis tools were used to predict the impact of novel mutations.Results:All cases had elevated serum levels of tetradecanoylcarnitine(C14:1)which is the characteristic biomarker for VLCADD.The phenotype of VLCADD is heterogeneous.Two patients were hospitalized for hypoactivity and hypoglycemia shortly after birth.Three patients showed hepatomegaly and hypoglycemia in infancy.The other two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis.Three of the patients died at the age of 6-8 months.Eleven different mutations in the ACADVL gene in the 7 patients were identified,including seven reported mutations(p.S22X,p.W427X,p.A213T,p.G222R,p.R450H,c.296-297delCA,c.1605+1G>T)and four novel mutations(p.S72F,p.Q100X,p.M437T,p.D466Y).The p.R450H and p.D466Y(14.28%,2/14 alleles)mutations were identifi ed in two alleles respectively.Conclusions:The clinical manifestations were heterogeneous and ACADVL gene mutations were heterozygous in the seven VLCADD Chinese patients.R450H may be a relatively common mutation in Asian populations.The genotype and phenotype had a certain correlation in our patients.
文摘目的探讨4例极长链酰基辅酶A脱氢酶(very long chain acyl-coenzyme A dehydrogenase,VLCAD)缺乏症的临床特征及基因变异特点。方法对新生儿筛查中十四烯酰基肉碱(C14:1)≥0.4μmol/L的新生儿召回复查,通过串联质谱、基因检测确诊4例VLCAD缺乏症患儿,对确诊患儿进行临床和基因变异分析。结果4例患儿血串联质谱结果中C14:1均特异性升高且首次召回复查值均低于初筛值,2例下降到正常范围,1例下降后仍>1μmol/L,1例仅轻微下降。4例患儿中共检出8种变异,以错义变异为主(5/8),并发现3种未报道过的新变异(p.Met344Val,p.Ala416Val,c.1077+6T>A)。均无明显异常临床表现。结论本研究结果扩宽了VLCAD缺乏症的基因谱,为临床VLCAD缺乏症的筛查和诊断提供了经验,为产前诊断提供了依据。
