CAJ | 학술논문

目的探讨极长链酰基辅酶A脱氢酶缺乏症(VLCADD)的临床表现,实验室检查特点以及基因型与表型的相关性.方法对2006年9月至2014年5月在上海新华医院儿科就诊的11例极长链酰基辅酶A脱氢酶缺乏症的临床表现、实验室检查、基因型、诊治和预后等进行分析.11例患儿中男9例、女2例,就诊年龄2d～17岁,诊断主要依靠血串联质谱和基因分析结合临床及其他检查.结果 11例均有血十四烯酰基肉碱(C14∶1)特异性升高.6例为新生儿早发型,3例为婴儿型,2例为成人迟发型.其中4例新生儿早发型和2例婴儿型在生后2～8个月死亡,目前存活的2例新生儿早发型患儿均通过新生儿疾病筛查得以早期诊断和治疗.11例中共检出17种ACADVL基因突变,检出率95.45％(21/22),包括11种已知突变(p.S22X,p.G43D,p.A213T,p.C215R,p.G222R,p.W427X,p.R450H,p.R456H,p.R511Q,c.296-297delCA,c.1605+ 1G＞T)和6种新突变(p.S72F,p.Q100X,p.M437T,p.D466Y,c.1315delG insAC,IVS7 +4 A＞G).p.R450H检出率最高,占总突变的13.63％ (3/22),其次为S22X和D466Y突变,各占9.09％(2/22).结论 11例VLCADD患儿的ACADVL基因突变谱具有高度异质性,新生儿型和婴儿型较成人迟发型患者死亡率高,提示基因型和表型间存在一定相关性.早期的诊断和治疗对患者的预后有重要意义.
목적 탐토겁장련선기보매A탈경매결핍증(VLCADD)적림상표현,실험실검사특점이급기인형여표형적상관성.방법 대2006년9월지2014년5월재상해신화의원인과취진적11례겁장련선기보매A탈경매결핍증적림상표현、실험실검사、기인형、진치화예후등진행분석.11례환인중남9례、녀2례,취진년령2d～17세,진단주요의고혈천련질보화기인분석결합림상급기타검사.결과 11례균유혈십사희선기육감(C14∶1)특이성승고.6례위신생인조발형,3례위영인형,2례위성인지발형.기중4례신생인조발형화2례영인형재생후2～8개월사망,목전존활적2례신생인조발형환인균통과신생인질병사사득이조기진단화치료.11례중공검출17충ACADVL기인돌변,검출솔95.45％(21/22),포괄11충이지돌변(p.S22X,p.G43D,p.A213T,p.C215R,p.G222R,p.W427X,p.R450H,p.R456H,p.R511Q,c.296-297delCA,c.1605+ 1G＞T)화6충신돌변(p.S72F,p.Q100X,p.M437T,p.D466Y,c.1315delG insAC,IVS7 +4 A＞G).p.R450H검출솔최고,점총돌변적13.63％ (3/22),기차위S22X화D466Y돌변,각점9.09％(2/22).결론 11례VLCADD환인적ACADVL기인돌변보구유고도이질성,신생인형화영인형교성인지발형환자사망솔고,제시기인형화표형간존재일정상관성.조기적진단화치료대환자적예후유중요의의.
Objective To investigate the clinical and laboratory features of very long chain acylCoA dehydrogenase deficiency (VLCADD) and the correlations between its genotype and phenotype.Method Eleven patients diagnosed as VLCADD of Shanghai Jiaotong University School of Medicine seen from September 2006 to May 2014 were included.There were 9 boys and 2 girls,whose age was 2 d-17 years.Analysis was performed on clinical features,routine laboratory examination,and tandem mass spectrometry (MS-MS),gas chromatography mass spectrometry (GC-MS) and genetic analysis were conducted.Result All cases had elevated levels of blood tetradecanoylcarnitine (C14∶1) recognized as the characteristic biomarker for VLCADD.The eleven patients were classified into three groups:six cases in neonatal onset group,three in infancy onset group form patients and two in late onset group.Neonatal onset patients were characterized by hypoactivity,hypoglycemia shortly after birth.Infancy onset patients presented hepatomegaly and hypoglycemia in infancy.The two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis.Six of the eleven patients died at the age of 2-8 months,including four neonatal onset and two infant onset patients,with one or two null mutations.The other two neonatal onset patients were diagnosed since early birth through neonatal screening and their clinical manifestation are almost normal after treatments.Among 11 patients,seventeen different mutations in the ACADVL gene were identified,with a total mutation detection rate of 95.45％ (21/22 alleles),including eleven reported mutations (p.S22X,p.G43D,p.R511Q,p.W427X,p.A213T,p.C215R,p.G222R,p.R450H,p.R456H,c.296-297delCA,c.1605 + 1G ＞ T) and six novel mutations (p.S72F,p.Q100X,p.M437T,p.D466Y,c.1315delG insAC,IVS7 + 4 A ＞ G).The p.R450H was the most frequent mutation identified in three alleles (13.63％,3/22 alleles),followed by p.S22X and p.D466Y mutations which were detected in two alleles (9.09％,2/22 alleles).Conclusion The ACADVL gene mutations were heterozygous in our patients.The mortality of neonatal onset form and infant onset form is much higher than the late onset form patients,suggesting a certain correlation between the genotype and phenotype was found.The earlier diagnosis and treatment of VLCADD are of vital importance for the improvement of the prognosis of the patients.