摘要
目的分析南京地区新生儿遗传代谢病的检出情况。方法分析2013年12月至2018年7月南京市出生的175767例串联质谱新生儿筛查的结果。采用非衍生化串联质谱技术检测干血滤纸片氨基酸、酰基肉碱和琥珀酰丙酮浓度,筛查新生儿氨基酸、有机酸和脂肪酸等三大类遗传代谢病。对于筛查阳性的患儿,通过基于高通量测序技术的基因Panel检测致病基因突变。对数据采用描述性统计学方法进行分析。结果175767例新生儿筛查初筛阳性率为2.1%(3691/175767),3691例初筛阳性中召回3598例,最终临床诊断遗传代谢病患儿62例,包括氨基酸代谢病35例、有机酸代谢病12例、脂肪酸代谢病15例。本地区新生儿遗传代谢病的总发病率为0.0353%,其中氨基酸代谢病、有机酸代谢病和脂肪酸代谢病的总发病率分别为0.0199%、0.0068%和0.0085%。发病率最高的疾病分别为苯丙氨酸羟化酶缺乏症0.0159%、甲基丙二酸血症0.0051%和原发性肉碱缺乏症0.0051%。62例临床诊断为遗传代谢病的患儿中,51例(82.2%,包括17例苯丙氨酸羟化酶缺乏症和34例其他遗传代谢病)进行了基因诊断(另外11例苯丙氨酸羟化酶缺乏症患儿拒绝进行基因诊断)。17例苯丙氨酸羟化酶缺乏症患儿均找到2个致病突变,分别来自于父母。34例其他遗传代谢病患儿中29例找到2个致病突变,分别来自于父母;另5例患儿仅找到1个致病突变,其中2例高甲硫氨酸血症为常染色体显性遗传。结论本地区发病率较高的新生儿遗传代谢病为苯丙氨酸羟化酶缺乏症、甲基丙二酸血症和原发性肉碱缺乏症。串联质谱筛查出的部分病例仅表现为筛查指标异常,随访中尚未出现特异性临床症状,需要进行更长期的随访。
Objective To analyze the detection of neonatal inherited metabolic diseases in Nanjing.Methods We researched the results of 175767 newborns by tandem mass spectrometry from December 2013 to July 2018.Amino acids,acylcarnitines,and succinylacetone were detected by non-derivatized tandem mass spectrometry to screen the abnormity of newborn amino acid,organic acid,or fatty acid oxidation metabolism disease.Gene panels based on high throughput sequencing technology were carried out to detect gene mutation of positive neonates.Descriptive statistics were used to analyze all the data.Results The positive rate of primary screening was 2.1%(3691/175767),3598 of 3691 positive cases were recalled.At last,62 cases of the inherited metabolic disease were diagnosed.Among them,there were 35 cases of amino acid metabolism disease,12 cases of organic acid metabolism disorder,and 15 cases of fatty acid metabolism defect.The total incidence of neonatal inherited metabolic disease was 0.0353%,among which amino acid metabolic diseases were 0.0199%,organic acid metabolic diseases were 0.0068%,and fatty acid metabolic diseases were 0.0085%.The diseases with the highest incidence were phenylalanine hydroxylase deficiency(0.0159%),methylmalonic acidemia(0.0051%),and primary carnitine deficiency(0.0051%).Among 62 children,51(82.2%)were diagnosed by gene diagnosis(including 17 cases of phenylalanine hydroxylase deficiency and 34 cases of other inherited metabolic diseases).Another 11 children with phenylalanine hydroxylase deficiency refused gene diagnosis.Two pathogenic mutations were found in 17 children with phenylalanine hydroxylase deficiency.Two pathogenic mutations were found in 29 of the other 34 children with inherited metabolic disease,which were from their parents,while only one pathogenic mutation was found in the other five children,of which two cases with hypermethioninemia were autosomal dominant inheritance.Conclusions Neonatal inherited metabolic diseases with high incidence in Nanjing are phenylalanine hydroxylase deficiency,methylmalonic acidemia,and primary carnitine deficiency.Some cases screened by tandem mass spectrometry only showed abnormal screening indicators.No specific clinical symptoms were found during follow-up,and further follow-up was needed.
作者
孙云
王彦云
马定远
张志蕾
程威
蒋涛
Sun Yun;Wang Yanyun;Ma Dingyuan;Zhang Zhilei;Cheng Wei;Jiang Tao(Genetic Medicine Center,Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University(Nanjing Maternity and Child Health Hospital),Nanjing 210004,China)
出处
《中华围产医学杂志》
CAS
CSCD
北大核心
2020年第4期224-231,共8页
Chinese Journal of Perinatal Medicine
基金
国家自然科学基金(81671475)
第二周期江苏省妇幼健康重点人才项目(FRC201747)。
关键词
新生儿筛查
遗传性疾病
先天性
代谢缺陷
先天性
突变
串联质谱法
Neonatal screening
Genetic diseases
inborn
Metabolism
inborn errors
Mutation
Tandem mass spectrometry
