目的 采用串联质谱(MSMS)技术筛查遗传代谢病情况并进行分析,明确嘉兴市遗传代谢病流行病学特点及基因变异谱,为预防新生儿出生缺陷提供科学依据。方法 对嘉兴市2015年1月—2022年12月出生的新生儿取足跟血采用MSMS法进行初筛,初筛阳性者予以召回复查并进行生化和基因检测,结合临床表现明确诊断,回顾性分析其发病率及基因变异。结果 2015—2022年全市活产新生儿为376 649名,总筛查人数375 562名,采用MSMS法筛查328 660名,平均筛查率为87.26%且逐年上升。确诊氨基酸代谢障碍(AAD)、脂肪酸β氧化障碍(FAOD)、有机酸代谢障碍(OAD)三大类疾病患儿85例,总发病率为1/3 867。高苯丙氨酸血症、原发性肉碱缺乏症和甲基丙二酸血症分别为AAD、FAOD和OAD中最常见的病种,发病率分别为1/14 290、1/21 911和1/54 777。基因分析共发现90种基因变异,最常见为PAH基因的c.728G>A、c.1068C>A和c.721C>T变异,ACADSB基因的c.1165G>A变异,SLC22A5基因的c.1400C>G、c.51C>G变异和SLC25A13基因的c.615+5G>A变异。结论 嘉兴市实现了对新生儿遗传代谢病的早期筛查和诊治,明确了该类疾病的发病率和基因变异谱,对加强出生缺陷防控、提高出生人口质量具有重大意义。
Abstract
Objective To analyze the profile of inborn errors of metabolism (IEM) using tandem mass spectrometry (MSMS) screening, and to clarify the epidemiological characteristics and genetic variant spectrum in Jiaxing City, in order to provide a scientific basis for the prevention of neonatal birth defects. Methods Heel blood samples from newborns born in Jiaxing City between January 2015 and December 2022 were initially screened by MSMS.Positive cases were recalled for retesting, followed by biochemical and genetic analyses.Diagnoses were confirmed based on clinical manifestations, and the incidence rates and genetic variants were retrospectively analyzed. Results Among 376 649 live births during the study period, 375 562 neonates were screened, with 328 660 undergoing MSMS screening (average screening rate: 87.26%, increasing annually).A total of 85 cases were diagnosed with amino acid disorders (AADs), fatty acid oxidation disorders (FAOD), or organic acid disorders (OAD), yielding an overall incidence of 1/3 867.Hyperphenylalaninemia, primary carnitine deficiency, and methylmalonic acidemia were the most prevalent conditions in AADs, FAODs, and OADs, with incidences of 1/14 290, 1/21 911, and 1/54 777, respectively.Genetic analysis identified 90 pathogenic variants, with the most frequent being PAH c.728G>A, c.1068C>A, and c.721C>T; ACADSB c.1165G>A; SLC22A5 c.1400C>G and c.51C>G; and SLC25A13 c.615+5G>A. Conclusions This study clarifies the incidence and genetic variant spectrum of neonatal IEM in the region, enabling early screening, diagnosis, and intervention in Jiaxing City.These findings are critical for strengthening birth defect prevention and improving neonatal health outcomes.
关键词
串联质谱技术 /
新生儿 /
遗传代谢病 /
基因变异谱
Key words
tandem mass spectrometry /
newborn /
inborn errors of metabolism /
gene variation spectrum
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参考文献
[1] 赵正言,顾学范.新生儿遗传代谢病筛查[M].北京:人民卫生出版社,2015.
Zhao ZY, Gu XF.Neonatal inherited metabolic disease screening[M].Beijing:People′s Medical Publishing House,2015.(in Chinese)
[2] Waters D, Adeloye D, Woolham D, et al.Global birth prevalence and mortality from inborn errors of metabolism: A systematic analysis of the evidence[J].J Glob Health,2018,8(2):021102.
[3] Saudubray J-M, Garcia-Cazorla A.An overview of inborn errors of metabolism afecting the brain: From neurodevelopment to neurodegenerative disorders[J].Dialogues Clin Neurosci,2018,20(4):301-25.
[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遗传代谢病筛查学组.新生儿遗传代谢病筛查组织管理及血片采集技术规范专家共识[J].中华新生儿科杂志,2023,38(6):321-326.
Screening Group of Neonatal Genetic Metabolic Disease, Special Committee of Birth Defects Prevention and Control, Chinese Preventive Medical Association.Consensus on the organizational management and dry blood sample collection for neonatal inherited metabolic disease screening[J].Chin J Neonatol, 2023,38(6):321-326.(in Chinese)
[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遗传代谢病筛查学组,国家卫生健康委员会临床检验中心新生儿遗传代谢病筛查室间质评专业委员会.新生儿遗传代谢病筛查实验室检测技术规范专家共识[J].中华新生儿科杂志(中英文),2023,38(8):449-454.
Screening Group of Neonatal Genetic Metabolic Disease,Special Committee of Birth Defects Prevention and Control,Chinese Preventive Medical Association, Newborn Genetic Metabolic Disease Screening Laboratory Quality Evaluation Professional Committee from Clinical Laboratory Center of National Health Commission.Consensus on laboratory testing technical guidelines of neonatal genetic metabolic disease screening[J].Chin J Neonatol,2023,38(8):449-454.(in Chinese)
[6] 胡真真,杨建滨,尚世强,等.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[J].中华检验医学杂志,2018,41(4):300-304.
Hu ZZ, Yang JB, Shang SQ,et al.Preliminary application of Region 4 Stork project used in newborn screening by tandem mass spectrometry[J].Chin J Lab Med,2018,41(4):300-304.(in Chinese)
[7] 李霞,何玲,孙玉亭,等.长沙地区352449例新生儿多种遗传代谢病的筛查结果分析[J].中华医学遗传学杂志,2023,40(9):1075-1085.
Li X, He L, Sun YT, et al.Analysis of screening results for genetic metabolic diseases among 352 449 newborns from Changsha[J].Chin J Med Gen,2023,40(9):1075-1085.(in Chinese)
[8] Zhang R,Qiang R,Song C, et al.Spectrum analysis of inborn errors of metabolism for expanded newborn screening in a northwestern Chinese population[J].Sci Rep,2021,11(1):2699.
[9] 顾学范,韩连书,余永国.中国新生儿遗传代谢病筛查现状及展望[J].罕见病研究,2022,01:13-19.
Gu XF, Han LS, Yu YG.Current status and prospects of screening for newborn hereditary metaboolic disease[J].Journal of Rare Diseases,2022,01:13-19.(in Chinese)
[10] 祁晓峰,张昊昱,李晓霞,等.1981—2019年河北省新生儿苯丙酮尿症的筛查分析[J].中国优生与遗传杂志,2021,29(2):241-242.
Qi XF, Zhang HY, Li XX, et al.Neonatal PKU screening in Hebei province: Analysis and thinking of results from 1981 to 2019[J].Chinese Journal of Birth Health & Heredity,2021,29(2):241-242.(in Chinese)
[11] 汪国庆,赵军,谭功军,等.珠海市2007—2019年新生儿先天性甲状腺功能减低症与苯丙酮尿症筛查结果分析[J].海南医学,2022,33(14):1832-1835.
Wang GQ, Zhao J, Tan GJ, et al.Screening analysis of congenital hypothyroidism and phenylketonuria in newborns from 2007 to 2019 in Zhuhai[J].Hainan Med J,2022,33(14):1832-1835.(in Chinese)
[12] 邓伟,丰琳,陈小凤.235 361例新生儿疾病筛查情况分析[J].中国继续医学教育, 2021,13(12):129-132.
Deng W, Feng L, Chen XF.Analysis of 235 361 cases of neonatal disease screening[J].China Continuing Medical Education,2021,13(12):129-132.(in Chinese)
[13] Wang X, Wang Y, Ma D, et al.Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population[J].Orphanet J Rare Dis, 2021, 16(1):214.
[14] Liu N, Huang Q, Li Q, et al.Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China[J].BMC Med Genet, 2017, 18(1):108.
[15] Ye J, Yang Y, Yu W, et al.Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: Results of a retrospective, multicentre study[J].J Inherit Metab Dis, 2013, 36(5):893-901.
[16] 郭冰冰,彭磊,李茜,等.徐州地区新生儿希特林蛋白缺乏症筛查和基因突变分析[J].中华新生儿科杂志,2022,37(2):97-103.
Guo BB, Peng L, Li Q, et al.Screening strategy and genetic mutation analysis of citrin deficiency among newborns in Xuzhou[J].Chin J Neonatol,2022,37(2):97-103.(in Chinese)
[17] 覃晓,旷娟,蓝国锋,等.南宁市部分地区新生儿遗传代谢病疾病谱和基因谱特征分析[J].中华新生儿科杂志(中英文),2023,38(5):289-293.
Qin X, Kuang J, Lan GF, et al.Disease spectrum and genetic profiles of neonatal inborn errors of metabolism in selected areas of Nanning city[J].Chin J Neonatol,2023,38(5):289-293.(in Chinese)
[18] Panmanee J, Antonyuk SV, Hasnain SS.Structural basis of the dominant inheritance of hypermethioninemia associated with the Arg264His mutation in the MAT1A gene[J].Acta Crystallogr D Struct Biol, 2020, 76(Pt 6):594-607.
[19] Li X, He J, He L, et al.Spectrum analysis of inherited metabolic disorders for expanded newborn screening in a central Chinese population[J].Front Genet,2021, 12:763222.
[20] 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.
[21] 宫丽霏,杨楠,赵金琦,等.北京市新生儿短链酰基辅酶A脱氢酶缺乏症筛查、临床特征及基因突变分析[J].浙江大学学报(医学版),2022,51(3):278-283.
Gong LF, Yang N, Zhao JQ, et al.Clinical characteristics and related gene mutations of infants with short-chain acyl-CoA dehydrogenase deficiency by neonatal screening in Beijing[J].Journal of Zhejiang University(Medical Sciences),2022,51(3):278-283.(in Chinese)
[22] Maguolo A, Rodella G, Dianin A, et al.Diagnosis, genetic characterization and clinical follow up of mitochondrial fatty acid oxidation disorders in the new era of expanded newborn screening: A single centre experience[J].Mol Genet Metab Rep, 2020,24: 100632.
[23] Keller Sa,Luciani A.Mitochondrial distress in methylmalonic acidemia: novel pathogenic insights and therapeutic perspectives[J].Cells,2022,11(19):3179.
[24] Lin YM,Gao HZ,Lin CM,et al.Biochemical,clinical,and genetic characteristics of short/branched chain Acyl-CoA dehydrogenase deficiency in Chinese patients by newborn screening[J].Front Genet,2019,28(10):802.
[25] 马雪,刘怡,陈哲晖,等.78例丙酸血症患者的基因型和表型分析[J].中华预防医学杂志,2022,56(9):1263-1271.
Ma X, Liu Y, Chen ZH, et al.Phenotypes and genotypes of 78 patients with propionic acidemia[J].Chin J Preventive Medicine,2022,56(9):1263-1271.(in Chinese)
基金
国家重点研发计划(2022YFC2703401)
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