Region 4 Stork系统在新生儿遗传代谢病串联质谱筛查中的初步应用  

Preliminary application of Region 4 Stork project used in newborn screening by tandem mass spectrometry

作　　者：胡真真 杨建滨[2] 尚世强[2] 黄新文 张玉[1] 胡凌微 吴鼎文 赵正言 Hu Zhenzhen;Yang Jianbin;Shang Shiqiang;Huang Xinwen;Zhang Yu;Hu Lingwei;Wu Dingwen;Zhao Zhengyan(Department of Genetics and Metabolism, Children＇s Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory for DiaGnosis and Therapy of Neonatal Diseases, Ministry of Education Key Laboratory of Reproductive Genetics, Hangzhou 310052, China)

机构地区：[1]浙江省新生儿疾病诊治重点实验室生殖遗传教育部重点实验室浙江大学医学院附属儿童医院遗传代谢科,杭州310052 [2]浙江省新生儿疾病诊治重点实验室生殖遗传教育部重点实验室浙江大学医学院附属儿童医院实验检验中心,杭州310052

出　　处：《中华检验医学杂志》2018年第4期300-304,共5页Chinese Journal of Laboratory Medicine

基　　金：国家重点研发计划（2017YFC1001701）;国家自然科学基金（81172681）;浙江省卫计委科研项目（2014KYA258）

摘　　要：目的探讨Region 4 Stork（R4S）系统应用于新生儿遗传代谢病串联质谱筛查的可行性。方法回顾性研究2015年5月至2016年4月浙江省新生儿疾病筛查中心（省中心）串联质谱筛查新生儿362 822例。按照筛查结果分为确诊病例组（83例）、阴性组（360 554例）及假阳性组（2 185例）3个组。应用R4S系统后分析工具结合传统判断规则分别对3组原始数据进行处理，并与传统切值判读结果进行比较。使用最小－最大标准化法比较省中心与R4S系统数据库健康人群串联质谱检测指标及相关比值的5个百分位数。结果应用R4S系统结合传统判断规则，阳性预测值由3.7%增加至8.3%，特异性由99.40%增加至99.75%，假阳性率则由0.6%降至0.2%。确诊病例组2例脯氨酸血症漏诊，1例β酮硫解酶缺乏症误诊。阴性组样本使用R4S系统后分析工具直接排除311 638例，剩余48 916例结合传统判断规则排除。假阳性组减少至897例。健康人群部分指标及相关比值的5个百分位数与R4S系统数据库存在差异。 结论应用R4S系统能够提高筛查效率，但也存在少量漏诊和误诊，大量阴性样本需结合传统判断规则进行排除，在国内的应用还需结合该地区健康人群范围进行优化。Objective To investigate the feasibility of Region 4 Stork （R4S） project used for newborn screening by tandem mass spectrometry in China. Methods This retrospective study was performed among 362 822 neonates screened by tandem mass spectrometry from May 2015 to April 2016 in Zhejiang newborn screening center. Infants were grouped by screening result category： 83 true positive eases, 360 554 true negative cases and 2 185 false positive cases. Raw data was uploaded into R4S website to perform postanalytical interpretive tools, then results were analyzed with interpretation rules. The comparisons of normal population percentiles were done at five selected percentiles between Zhejiang newborn screening center and R4S project with rain-max normalization. Results Compared with cutoff system by using R4S project with interpretation rules, the positive predictive value increased from 3.7% to 8. 3%, the specificity increased from 99. 40% to 99. 75% , and the false positive rate declined from 0. 6% to 0. 2%. The two cases of true positive hyperprolinemia were reported negative, and one case of β-ketothiolase deficiency was misdiagnosis. Totally 311 638 cases in true negative group were resolved by postanalytieal interpretive tools, and the remaining 48 916 cases were excluded with interpretation rules. False positive cases were reduced to 897 cases. Results of percentiles comparison showed that levels of some markers were significantly different between zhejiang newborn screening center and R4S project. Conclusions R4S project effectively improved the newborn screening perforumnee, whereas leaded to a small number ofmisdiagnosis and missed diagnosis. Besides, many true negative cases should be excluded with interpretation rules. Optimization should be achieved based on local normal population.

关 键 词：代谢缺陷 先天性 串联质谱法 新生儿筛查 假阳性反应 

分 类 号：R446[医药卫生—诊断学] R722.1[医药卫生—临床医学]