Region 4 Stork系统在串联质谱新生儿极长链酰基辅酶A脱氢酶缺乏症筛查中的应用  

Application of Region 4 Stork system in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency by tandem mass spectrometry

作　　者：张超 胡真真[1] 杨建滨[1] 尚世强[2] 黄新文[1] 杨茹莱[1] 胡凌微 张玉 吴鼎文[1] 赵正言[1] Zhang Chao;Hu Zhenzhen;Yang Jianbin;Shang Shiqiang;Huang Xinwen;Yang Rulai;Hu Lingwei;Zhang Yu;Wu Dingwen;Zhao Zhengyan(Department of Genetics and Metabolism,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Lab Center,the Children′s Hospital,Zhejiang University School of Medicine,Hangzhou 310052,China;Zhejiang Biosan Biochemical Technologies Co.,Ltd,Hangzhou 310012,China)

机构地区：[1]浙江大学医学院附属儿童医院遗传与代谢科/国家儿童健康与疾病临床医学研究中心,杭州310052 [2]浙江大学医学院附属儿童医院实验检验中心,杭州310052 [3]浙江博圣生物技术股份有限公司,杭州310012

出　　处：《中华检验医学杂志》2020年第10期978-983,共6页Chinese Journal of Laboratory Medicine

基　　金：国家重点研发计划(2018YFC1002200,2017YFC1001701);浙江省科技厅公益技术研究计划(LGC19B050013)。

摘　　要：目的探讨国际协作的新生儿筛查数据平台Region 4 Stork(R4S)系统联合切值法分析应用于新生儿极长链酰基辅酶A脱氢酶缺乏症(VLCADD)串联质谱筛查的可行性。方法回顾性分析2013年10月至2018年7月浙江省新生儿疾病筛查中心2040072名新生儿应用串联质谱技术筛查的数据,使用R4S系统对其中依据传统切值法判别疑似VLCADD阳性的910例样本原始数据进一步分析,以临床诊断及ACADL基因检测结果为依据,统计比较两者的筛查效率。结果切值法判读的疑似VLCADD阳性910例数据经R4S系统进一步分析后,阳性判读减至238例(含9例确诊阳性),确诊患儿ACADL基因测序共发现16种不同变异。假阳性率由0.44‰(901/2040072)降至0.11‰(229/2040072),阳性预测值由0.99%(9/910)增至3.78%(9/238),筛查特异度由99.96%(2039162/2040063)增至99.99%(2039834/2040063)。切值法单独应用与联合R4S系统分析两者阳性率有统计学差异(χ²=393.5,P<0.05)。结论R4S系统联合切值法应用于串联质谱VLCADD新生儿筛查可显著提高筛查性能,降低假阳性率,具有一定的临床应用价值。Objective To investigate the application feasibility of Region 4 Stork(R4S)system,an international collaborative newborn screening data platform,combined with cut-off value analysis in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency(VLCADD)by tandem mass spectrometry(MS/MS).Methods The retrospective study was performed in 2,040072 neonates screened by MS/MS in Neonatal Screening Center of Zhejiang Province,China from October 2013 to July 2018.Nine hundred and ten cases were determined and identified as suspected positive VLCADD neonates by traditional cut-off method of tandem mass spectrometry.The original data of these 910 screened neonates were further analyzed by R4S system.Based on clinical diagnosis and ACADL gene test results,the screening efficiency between two methods was statistically compared.Results The data of 910 suspected VLCADD-positive cases interpreted by cut-off method were further analyzed by R4S system,and the positive interpretation was reduced to 238 cases(including 9 confirmed positive cases).A total of 16 different mutations were found in ACADL gene sequencing among the confirmed children.The screening false positive rate(FPR)declined from 0.44‰(901/2040072)to 0.11‰(229/2040072),the rate of positive predictive value(PPV)increased from 0.99%(9/910)to 3.78%(9/238),and the specificity increased from 99.96%(2039162/2040063)to 99.99%(2039834/2040063).There was a statistically significant difference between cut-off method alone and cut-off method combined R4S system analysis(χ²=393.5,P<0.05).Conclusions The R4S system combined with cut-off method applied in VLCADD neonatal screening by MS/MS can effectively improve screening performance,reduce false positive rate,and has certain value in clinical application.

关 键 词：新生儿筛查 新生儿疾病筛查 切值 串联质谱 数据平台 国际协作 假阳性率 临床诊断 

分 类 号：R722.1[医药卫生—儿科]