珠海地区新生儿遗传代谢病串联质谱筛查正常参考区间建立的临床研究  

Establishment of reference interval for neonatal genetic metabolic diseases screening by tandem mass spectrometry in Zhuhai

作　　者：汪国庆[1] 林萃[1] 吕晓萍[1] 谭功军 周玉球[1] WANG Guo-qing;LIN Cui;LYU Xiao-ping(Zhuhai Center for Maternal and Child Health care,Zhuhai 519000,China)

机构地区：[1]珠海市妇幼保健院,519000

出　　处：《中国实用医药》2023年第23期42-48,共7页China Practical Medicine

基　　金：珠海市科技计划项目(项目编号:ZH_(2)2036201210167PWC)。

摘　　要：目的 研究建立珠海地区正常新生儿干血斑样本中11种氨基酸和31种肉碱含量的参考区间,为新生儿遗传代谢病串联质谱筛查的结果解读提供理论依据。方法 20364例新生儿干血斑样本,采用串联质谱技术对其11种氨基酸和31种肉碱含量进行检测,按纳入标准选取18542例新生儿筛查数据,以百分位数法(P_(0.5)~P_(99.5))统计参考区间;采用摘要独立样本t检验比较珠海地区串联质谱检测结果与中国临床机构检测结果的差异;Wilcoxon秩和检验比较珠海地区串联质谱参考区间与上海新华医院的差异。结果 20364例新生儿初筛阳性687例,召回621例,确诊遗传代谢病7例,其中原发性肉碱缺乏症2例, citrin蛋白缺乏症、高甲硫氨酸血症、甲基丙二酸血症、中链酰基辅酶A脱氢酶缺乏症和极长链酰基辅酶A脱氢酶缺乏症各1例。氨基酸代谢病、有机酸代谢病、脂肪酸氧化障碍的发病率分别为0.010%(1/10182)、0.005%(1/20364)和0.020%(1/5091),总发病率为0.034%(1/2909)。18542例新生儿11种氨基酸检测结果与中国临床机构检测结果比较,差异均有统计学意义(P<0.001);18542例新生儿31种肉碱中除异戊烯酰肉碱(C5:1)、己酰肉碱(C6)、辛酰肉碱(C8)、癸二烯酰肉碱(C10:2)、肉豆蔻二烯酰肉碱(C14:2)、3-羟基棕榈酰肉碱(C16OH)、3-羟基棕榈烯酰肉碱(C16:1OH)、3-羟基十八碳酰肉碱(C18OH)、3-羟基十八碳烯酰肉碱(C18:1OH)等指标外,其余肉碱检测结果与中国临床机构检测结果比较,差异均有统计学意义(P<0.001)。珠海地区新生儿丙氨酸(Ala)、甘氨酸(Gly)、亮氨酸(Leu)、鸟氨酸(Orn)、苯丙氨酸(Phe)、酪氨酸(Tyr)、缬氨酸(Val)、游离肉碱(C0)、己二酰肉碱(C6DC)参考区间下限与新华医院新生儿比较,差异有统计学意义(P<0.05)。结论 珠海地区新生儿遗传代谢病串联质谱筛查11种氨基酸和31种肉碱参考区间的建立,为本地区新生儿遗传代谢病串联质谱筛�Objective To establish the reference interval for the content of 11 amino acids and 31 carnitine in normal neonatal dry blood spot samples in Zhuhai,in order to provide theoretical basis for the interpretation of the screening results of genetic metabolic diseases in neonates.Methods The contents of 11 amino acids and 31 carnitine in 20364 neonatal dry blood spot samples were detected by tandem mass spectrometry.The screening data of 18542 neonates were selected according to the inclusion criteria,and the reference interval was analyzed by percentile method(P_(0.5)~P_(99.5)).Summary independent sample t-test was used to compare the difference between the results of tandem mass spectrometry in Zhuhai and those of Chinese clinical institutions.Wilcoxon rank-sum test was used to compare the difference between the reference interval of tandem mass spectrometry in Zhuhai and Shanghai Xinhua Hospital.Results A total of 20364 neonates were screened,687 cases were positive at initial screening,621 cases were recalled,and 7 cases were diagnosed with genetic metabolic diseases,including 2 cases of primary carnitine deficiency,1 case of citrin protein deficiency,1 case of hypermethioninemia,1 case of methylmalonic acidemia,1 case of medium-chain acyl-coA dehydrogenase deficiency and 1 case of very long-chain acyl-CoA dehydrogenase deficiency.The incidence of amino acid metabolic disease,organic acid metabolic disease and fatty acid oxidation disorder were 0.010%(1/10182),0.005%(1/20364)and 0.020%(1/5091),respectively.The total incidence was 0.034%(1/2909).The results of 11 amino acids in 18542 neonates were compared with those of Chinese clinical institutions,and the differences were statistically significant(P<0.001).Among the 31 carnitine in 18542 neonates,except for isopentenylcarnitine(C5:1),hexyl carnitine(C6),capryloylcarnitine(C8),decadienoylcarnitine(C10:2),tetradecadienoylcarnitine(C14:2),3-hydroxypalmitoylcarnitine(C16OH),3-hydroxypalmitoleylcarnitine(C16:1OH),3-hydroxystearoylcarnitine(C18OH),and 3-hydroxyoleylca

关 键 词：遗传代谢病 串联质谱筛查 参考区间 

分 类 号：R722.1[医药卫生—儿科]