南通地区新生儿高苯丙氨酸血症研究结果分析

Analysis the results of neonatal hyperphenylalanine in Nantong city

目的探讨南通市新生儿疾病筛查中心2014年5月—2018年4月间168 800例新生儿高苯丙氨酸血症患病情况,分析本地区高苯丙氨酸血症(HPA)基因分布特点。方法应用茚三酮荧光法对168 800例新生儿进行筛查,将筛查阳性者进行串联质谱检测,同时做尿蝶呤检测、红细胞二氢喋啶还原酶测定和基因诊断。结果 HPA患儿共确诊27例,其中1例为BH4血症。初筛阳性人数是335例,其中已召回318例,召回率是94.93%,初筛阳性率是0.198%,阳性预测值是8.18%。患病率是0.0154%(26/168 800),明显高于全国和江苏省患病率。同时基因检测结果显示南通地区基因突变主要出现在第7号外显子,以R243Q突变频率最高,占了17.857%。这符合中国人的苯丙氨酸羟化酶基因(PAH)特点。结论南通地区新生儿高苯丙氨酸血症的发病率较高,通过新生儿筛查可以及早发现、及早干预,对控制患儿病情发展有一定的帮助。同时明确了南通地区新生儿高苯丙氨酸血症的基因主要的突变位置在7号外显子上,以R243Q突变频率最高,因此明确的基因型对患儿疾病分型、诊断也有重要意义。

Objective:Investigate the prevalence of 168 800 cases of neonatal hyperphenylalaninemia in Nantong Neonatal Disease Screening Center from May 2014 to April 2018,and to analyze the gene distribution characteristics of hyperphenylalaninemia(HPA).Methods:Ninhydrin fluorescence method was used to screen 168 800 neonates.The positive neonates were detected by tandem mass spectrometry,urinary pterin,erythrocyte dihydropterin reductase and gene diagnosis.Results:A total of 27 cases of HPA were diagnosed,of which 1 were BH4.Among 335 positive cases,318 cases were recalled,the recall rate was 94.93%,the positive rate of primary screening was 0.198%,and the positive predictive value was 8.18%.The prevalence rate was 0.0154%(26/168 800),which was significantly higher than that in the whole country and Jiangsu province.At the same time,gene mutation mainly occurred in Exon 7 in Nantong city,and R243Q mutation frequency was the highest,accounting for 17.857%.This is consistent with the Chinese phenylalanine hydroxylase gene(PAH).Conclusion:The incidence of neonatal hyperphenylalanine is high in Nantong city.Early detection and intervention can be achieved by neonatal screening,which is helpful to control the development of the disease.At the same time,it is clear that the main mutation site of the gene of neonatal hyperphenylalanine in Nantong city is exon 7,and R243Q mutation frequency is the highest,so the clear genotype is also of great significance to the classification and diagnosis of the disease in children.