20 307例黎族新生儿多种遗传代谢性疾病筛查研究

背景　遗传代谢性疾病虽单一病种发病率低，但总体发病率在新生儿中可达0.5%。海南属于贫困落后地区，黎族人群又聚集在海南贫困偏远山区，在黎族新生儿中筛查遗传代谢性疾病可为黎族同胞为该病的诊疗提供实验诊断支持，预防黎族人群出生缺陷，提高人口素质，同时可起到健康扶贫的作用。目的　调查海南省黎族新生儿遗传代谢性疾病的发病情况。方法　收集海南省2016年10月-2018年9月出生的黎族新生儿20 307例干血片样本，使用PE公司生产的非衍生化多种氨基酸、肉碱和琥珀酰丙酮测定试剂盒（串联质谱法）进行串联质谱筛查11种氨基酸、1种游离肉碱和30种酰基肉碱，初筛可疑样本召回复查，复筛异常者送血样本至北京迈基诺基因公司做基因诊断。结果　20 307例新生儿中初筛异常840例，初筛异常率为4.14%（840/20 307）。随访死亡5例，召回835例，复查后排除770例，疑似遗传代谢性疾病65例，确诊遗传代谢性疾病12例，发病率为59/10万（12/20 307）。12例遗传代谢性疾病中，原发肉碱缺乏症（PCD）5例，苯丙酮尿症（PKU）3例，3-甲基巴豆酰辅酶A羧化酶缺乏症（MCCD）2例，甲基丙二酸血症（MMA）1例，丙二酸血症（MAD）1例。5例PCD发现3种基因突变：1例c.760C>T、2例c.51C>G和2例c.338G>A。3例PKU发现3种基因突变：c.1081A>T、c.728G>A和c.764T>C。2例MCCD基因突变位点均为c.1331G>A。MMA基因突变位点为c.456delT。MAD基因突变位点为c.541G>A。结论　海南省黎族新生儿遗传代谢性疾病发病率高，为59/10万，特别是PCD发病率最高，为1/4 061，串联质谱筛查多种遗传代谢性疾病具有重要意义。

Screening of Multiple Inherited Metabolic Diseases in 20307 Newborns of Li Ethnic Group

Background Although the incidence of a single inherited metabolic disease is low,the total incidence of all inherited metabolic diseases can reach 0.5%in newborns.Hainan is a poor and backward area,and the Li population gather in the poor and remote mountainous areas of Hainan province.Screening inherited metabolic diseases in the newborns of Li ethnic group can provide support for experimental diagnosis of these diseases to Li siblings,prevent birth defects of the Li population,improve population quality,and can play a role in health and poverty alleviation at the same time.Objective To investigate the incidence of inborn error of metabolism(IEM)of Li ethnic group’s newborns in Hainan Province.Methods A total of 20307 samples of dried blood samples from Li ethnic group’s newborns who were born in Hainan Province from October 2016 to September 2018 were collected.The Neo BaseTM Non-derivatized MSMS kits produced by PE were used.for screening 11 kinds of amino acids,a kind of free carnitine and 30 kinds of acylcarnitines by tandem mass spectrometry.The suspicious samples after primary screening were recalled and screened again,and after second screening,the still abnormal blood samples were sent to Beijing Maikeno gene company for genetic diagnosis.Results Among the 20307 newborns,the abnormal cases were 840 in the primary screening,and the abnormal rate was 4.14%(840/20307).Among the 840 cases,five patients who were followed updied and 835 patients were recalled.After reexaminnation,770 cases were excluded,65 cases were suspected IEM patients,and 12 cases were diagnosed with IEM by genetic diagnosis,and the incidence was 59/100000(13/20307).Among the 12 cases,5 cases were primary carnitine deficiency(PCD),3 cases were phenylketonuria(PKU),2 cases were 3-methylcrotonyl-coenzyme A carboxylase deficiency(MCCD),1 case was methylmalonic acidemia(MMA),and 1 case was malonic acidemia.3 types of gene mutation were found in 5 cases of PCD patients and among them,1 case was c.760 C>T,2 cases were c.51 C>G and 2 cases were c.338 G>A.Three types of gene mutation were found in 3 cases of PKU patients and they were c.1081 A>T,c.728 G>A and c.764 T>C respectively.The gene mutation site of the 2 MCCD patients was c.1331 G>A.The gene mutation site of the MMA patient was c.456 del T.And the gene mutation site of the malonic acidemia patient was c.541 G>A.Conclusion The incidence of IEM is high(59/100000)in the newborns of Li ethnic group in Hainan Province,especially PCD of which the incidence is the highest(1/4061).Screening of multiple genetic metabolic diseases by tandem mass spectrometry is of great significance.