目的 建立宁夏地区新生儿遗传代谢病串联质谱筛查中氨基酸、有机酸、脂肪酸切值(cut-off值)的范围,为本地新生儿遗传代谢病的筛查提供理论依据。方法 利用串联质谱技术非衍生法,使用两个批次的试剂盒和美国CDC质控品做质控,对宁夏地区符合筛查纳入标准的45 602例活产新生儿进行多种遗传代谢病检测;采用百分位数法制定宁夏地区氨基酸、有机酸、脂肪酸的cut-off值,第1百分位数(P₁)为低值阳性,第99百分位数(P₉₉)为高值阳性;Wilcoxon秩和检验比较宁夏地区串联质谱切值与上海新华医院的差异。结果 串联质谱筛查新生儿45 602例,确诊阳性病例31例,其中高苯丙氨酸血症 20例,枫糖尿症1例,高甲硫氨酸血症2例,瓜氨酸血症Ⅰ型1例,甲基丙二酸血症 3例,异戊酸血症1例,短链酰基辅酶A脱氢酶缺乏症1例,中链酰基辅酶A脱氢酶缺乏症1例,肉碱棕榈酰转移酶Ⅱ缺乏症 1例。宁夏地区新生儿串联质谱切值与上海新华医院相比,精氨酸(ARG)、甘氨酸(GLY)、酪氨酸(TYR)、鸟氨酸(ORN)、亮氨酸(LEU)、缬氨酸(VAL)、异戊酰肉碱(C5)、 十二碳酰肉碱(C12)、C0/(C16+C18)等检测指标差距较大。结论 随着筛查数量的不断增加及筛查范围的不断扩大,逐步积累筛查经验和阳性预测值,对宁夏地区新生儿遗传代谢病串联质谱筛查的cut-off值进行相应调整。

Objective To establish the cut-off value of amino acids, organic acids and aliphatic acids for newborn genetic metabolic disease screening in Ningxia, in order to provide theoretical basis for the laboratory diagnosis of neonate genetic metabolic diseases. Methods With non-derivative pretreatment of dry blood spots sample, tandem mass spectrometry method was adopted to detect amino acids, organic acids and aliphatic acids concentration in the whole blood samples of 45 602 neonates up to standard in Ningxia.Quality control products were from the two batches of kit and the U.S.centers for disease control.The percentile method was used to establish the cut-off value and identified P₁~P₉₉ as normal reference range.Wilcoxon rank sum test was performed to analyze the difference of cut-off value between Ningxia and Shanghai Xinhua hospital. Results Among 45 602 neonates who were screened,31 cases were diagnosed as postive,20 cases with HPA,1 case with MSUD,2 case with high methionine anemia,1 case with CTLN1,3 case with MMA,1 case with IVA,1 case with SCADD,1 case with MCAD,1 case with CPTII. Compared with the cut-off value of Shanghai Xinhua Hospital, the measurements of arginine,glycine,tyrosine,ornithine,leucine,valine,lsopentyl carnitine,twelve corbonyl carnitine,C0/(C16+C18) and so on were significautly different. Conclusion With the number of screening increasing and the range of screening expanded, more experience and positive predictive value will be accumulated to adjust the cut-off value of relevant measurements.