新生儿筛查发现的游离肉碱降低33例分析及临床随访  

Analysis and clinical follow-up of 33 cases of free carnitine decrease found in neonatal screening

作　　者：汪小霞 方海宁 汪鸿 WANG Xiaoxia;FANG Haining;WANG Hong(Department of Endocrinology,Genetics and Metabolism of Children,Hubei Maternal and Child Health Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430000,China;Department of Child Healthcare,Hubei Maternal and Child Health Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430000,China)

机构地区：[1]华中科技大学同济医学院附属湖北妇幼保健院儿童内分泌遗传代谢科,湖北武汉430000 [2]华中科技大学同济医学院附属湖北妇幼保健院儿童保健科,湖北武汉430000

出　　处：《中国优生与遗传杂志》2023年第7期1397-1401,共5页Chinese Journal of Birth Health & Heredity

基　　金：湖北省卫生健康委员会联合基金项目青年人才项目(WJ2019H291)。

摘　　要：目的了解湖北省妇幼保健院游离肉碱降低所致的遗传代谢病病种分布特征、发病率、基因突变特征及确诊病例的临床转归。方法对2017年12月至2022年9月在湖北省妇幼保健院新筛中心应用串联质谱技术进行筛查的新生儿205876例,完善酰基肉碱谱检测,初筛阳性者召回复查,仍阳性者同时检测患儿母亲游离肉碱,行高精准度二代测序技术明确诊断,并对确诊病例进行临床随访。结果在205876例新生儿中,初筛游离肉碱降低33例,其中原发性肉碱缺乏症15例,母源性肉碱缺乏症6例,SLC22A5基因携带者6例,假阳性5例,继发性肉碱缺乏1例,1例失访。检测到16种SLC22A5基因突变,热点突变是c.1400C>G和c.51C>G,首次报道了c.403G>A和c.1540G>C这种新发突变。结论新生儿串联质谱筛查是识别包括原发性肉碱缺乏症在内的遗传代谢病的有效方法,新生儿筛查游离肉碱降低最常见于原发性肉碱缺乏症,但也可以由其他代谢性疾病所继发,结合基因分析有助于明确诊断,并需排除假阳性及假阴性。我们的发现丰富了以游离肉碱降低为生化表现的遗传代谢病病种及基因突变谱,并为家系遗传咨询及产前诊断提供依据。Objective To understand the distribution characteristics,incidence rate,gene mutation characteristics and clinical outcomes of confirmed cases of genetic metabolic diseases caused by reduced free carnitine in Hubei Maternal and Child Health Hospital.Methods From December 2017 to September 2022,205876 neonates screened by tandem mass spectrometry in the new screening center of Hubei Maternal and Child Health Hospital were improved in acyl carnitine spectrum detection.Those who were initially screened positive were recalled for reexamination.The free carnitine of their mothers whose children were still positive were also reexamined.High-precision second generation sequencing technology were improved to make clear the diagnosis.The confirmed cases were followed up.Results Among 205876 neonates,33 had a decrease in free carnitine,including 15 cases of primary carnitine deficiency,6 cases of maternal carnitine deficiency,6 cases of SLC22A5 gene carriers,5 cases of false positive,1 case of secondary carnitine deficiency and 1 case of lost follow-up.Sixteen SLC22A5 gene mutations were detected,and the hot spot mutations were c.1400C>G and c.51C>G.The new mutations of c.403G>A and c.1540G>C were reported for the first time.Conclusion Neonatal tandem mass spectrometry screening is an effective method to identify genetic metabolic diseases including primary carnitine deficiency.The decrease of free carnitine in neonatal screening is most common in primary carnitine deficiency,but it can also be secondary to other metabolic diseases.Gene analysis is helpful to make a definite diagnosis,and false positive and false negative should be excluded.Our findings enrich the disease species and gene mutation spectrum of genetic metabolic diseases with low free carnitine as biochemical manifestation,and provide basis for genetic counseling and prenatal diagnosis of families.

关 键 词：新生儿原发性肉碱缺乏症筛查 游离肉碱 母源性肉碱缺乏 脂肪酸氧化代谢障碍 肉碱棕榈酰转移酶-Ⅱ缺乏症 

分 类 号：R722.1[医药卫生—儿科]