目的 了解四川省部分地区新生儿遗传代谢性疾病(IMDs)的发病率及病种情况,为确定筛查方案及政府制定相关政策提供依据。方法 采用串联质谱技术(非衍生法)对四川省部分地区39 648例新生儿进行遗传代谢病筛查,初筛异常样本召回复查,复查异常者送检尿有机酸及基因分析确诊。结果 共筛查新生儿39 648例,其中初筛异常1 594例,初筛阳性率为4.02%,最终确诊遗传代谢病9种共15例,总阳性预测值为1.05%,总发病率为1∶2 643。确诊病种包括短链酰基辅酶A脱氢酶缺乏症5例,原发性肉碱缺乏症2例,甲基丙二酸血症2例,丙酸血症1例,异戊酸血症1例,2-甲基丁酰甘氨酸尿症1例,3-甲基巴豆酰辅酶A羧化酶缺乏症1例,苯丙氨酸羟化酶缺乏症1例,Citrin缺乏致新生儿肝内胆汁淤积症1例。结论 四川省部分地区IMDs病种多样,发病率较高;短链酰基辅酶A脱氢酶缺乏症为本地区最常见的IMDs;串联质谱筛查对IMDs的早期发现及诊治具有非常重要的意义。
Abstract
Objective To explore the incidence and disease spectrum of neonatal inherited metabolic disorders (IMDs) in parts of Sichuan,so as to provide basis for determining the screening programs and making relevant policies by the government in future. Methods A total of 39 648 newborns in Sichuan were screened for IMDs by tandem mass spectrometry (non-derivative method),and the samples with abnormal initial screening results were recalled for reexamination.Those with abnormal reexamination results would be diagnosed by urine organic acid and gene analysis. Results A total of 39 648 newborns were screened,1 594(4.02%) of whom were abnormal in the initial screening.Eventually,9 kinds of 15 cases of IMDs were diagnosed,and the total positive predictive value was 1.05%,the total incidence was 1∶2 643.The confirmed diseases included 5 cases of short-chain acyl-CoA dehydrogenase deficiency(SCADD),2 cases of primary carnitine deficiency(PCD),2 cases of methylmalonic acidemia(MMA),1 case of propionic acidemia(PA),1 case of isovaleric acidemia(IVA),1 case of 2-methylbutyrylglycinuria(MBCD),1 case of 3-methylcrotonyl CoA carboxylase deficiency(MCCD),1 case of phenylalanine hydroxylase deficiency(PKU),1 case of neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD). Conclusion s There are many kinds of IMDs with higher incidence in parts of Sichuan,of which short-chain acyl-CoA dehydrogenase deficiency is the most common.Therefore,newborn screening by tandem mass spectrometry is of great significance for the early detection and diagnosis of IMDs.
关键词
串联质谱 /
遗传代谢性疾病 /
新生儿疾病筛查 /
先天性疾病
Key words
tandem mass spectrometry /
inherited metabolic disorders /
newborn screening /
congenital disease
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 顾学范.临床遗传代谢病[M].北京:人民卫生出版社,2015:1.
[2] 中华人民共和国卫生部.新生儿疾病筛查技术规范(2010版)[S].2010-11-27.
[3] 中华医学会儿科学分会内分泌遗传代谢学组,中华预防医学会出生缺陷预防与控制专业委员会新生儿筛查学组.高苯丙氨酸血症的诊治共识[J].中华儿科杂志,2014,52(6):420-425.
[4] 中华预防医学会出生缺陷预防与控制专业委员会新生儿筛查学组,中华医学会儿科学分会临床营养学组,中国医师协会医学遗传医师分会临床生化遗传专业委员会,等.苯丙氨酸羟化酶缺乏症饮食治疗与营养管理共识[J].中华儿科杂志,2019,57(6):405-409.
[5] 中华预防医学会出生缺陷预防与控制专业委员会新生儿筛查学组,中华医学会儿科学分会临床营养学组,中华医学会儿科学分会内分泌遗传代谢学组,等.单纯型甲基丙二酸尿症饮食治疗与营养管理专家共识[J].中国实用儿科杂志,2018,33(7):481-486.
[6] 中华预防医学会出生缺陷预防与控制专业委员会新生儿遗传代谢病筛查学组,中华医学会儿科分会出生缺陷预防与控制专业委员会,中国医师协会医学遗传医师分会临床生化遗传专业委员会,等.原发性肉碱缺乏症筛查与诊治共识[J].中华医学杂志,2019,99(2):88-92.
[7] Lindner M,Gramer G,Haege G,et al.Efficacy and outcome of expanded newborn screening for metabolic diseases-report of 10 years from South-West Germany[J].Orphanet J Rare Dis,2011,6:44.
[8] Couce ML,Castiñeiras DE,Bóveda MD,et al.Evaluation and long-term follow-up of infants with inborn errors of metabolism identified in an expanded screening programme[J].Mol Genet Metab,2011,104:470-475.
[9] Kasper DC,Ratschmann R,Metz TF,et al.The National Austrian Newborn Screening Program- Eight years experience with mass spectrometry.Past,present,and future goals[J].Wien Klin Wochenschr,2010,122:607-613.
[10] Frazier DM,Millington DS,McCandless SE,et al.The tandem mass spectrometry newborn screening experience in North Carolina:1997-2005[J].J Inherit Metab Dis,2006,29(1):76-85.
[11] Jane E,Wilcken B,Carpenter C,et al.Expanded newborn screening in New South Wales:missed cases[J].J Inherit Metab Dis,2014,37:881-887.
[12] Yamaguchi S.Newborn screening in Japan:restructuring for the newera[J].Ann Acad Med Singap,2008,37(Suppl 12):13-15.
[13] Yoon HR,Lee KR,Kang S,et al.Screening of newborns and high-risk group of children for inborn metabolic disorders using tandem mass spectrometry in South Korea:a three-year report[J].Clin Chimacta,2005,354:167-180.
[14] Lim JS,Tan ES,John CM,et al.Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS):an 8 year journey from pilot to current program[J].Mol Genet Metab,2014,113:53-61.
[15] Shi XT,Cai J,Wang YY,et al.Newborn screening for inborn errors of metabolism in mainland China:30 years of experience[J].JIMD Reports,2012,6:79-83.
[16] Guo KJ,Zhou X,Chen XG,et al.Expanded newborn ac reening for inborn errors of metabolism and genetic characteristics in a Chinese population[J].Front Genet,2018,9:122.
[17] 黄新文,杨建滨,童凡,等.串联质谱技术对新生儿遗传代谢病的筛查及随访研究[J].中华儿科杂志,2011,49(10):765-770.
[18] Niu DM,Chien YH,Chiang CC,et al.Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan[J].J Inherit Metab Dis,2010,33(Suppl 2):295-305.
[19] Yang YQ,Wang LL,Wang BJ,et al.Application of next-generation sequencing following tandem mass spectrometry to expand newborn screening for inborn errors of metabolism:a multicenter study[J].Front Gent,2019,10:86.
[20] Lin YM,Zheng QZ,Zheng TW,et al.Expanded newborn screening for inherited metabolic disorders and genetic characteristics in a southern Chinese population[J].Clin Chimacta,2019,494:106-111.
[21] 裴薇,鹿相花,田维兵,等.潍坊地区新生儿遗传代谢病串联质谱筛查结果分析[J].中国中西医结合儿科学,2018,10(5):452-455.
[22] Wilcken B,Wiley V,Hammond J,et al.Screening newborns for inborn errors of metabolism by tandem mass spectrometry[J].New Engl J Med,2003,348:2304-2312.
PDF(654 KB)
