摘要目的 分析河南省新生儿原发性肉碱缺乏症(primary carnitine deficiency,PCD)的患病率、临床特征和基因突变特点,为PCD的早期诊断、治疗以及遗传咨询和产前诊断提供依据.方法 采用串联质谱分析技术,对2013年1月至2017年12月河南省的720 667例新生儿进行遗传代谢病筛查,对初筛可疑阳性的新生儿母亲进行串联质谱检查,对确诊PCD病例及家系进行肉碱转运蛋白SLC22A5基因突变检测验证,对确诊病例分析其临床、生化改变及基因突变特点,进行补充左旋肉碱及饮食指导,随访观察其生长发育情况.结果 共确诊PCD新生儿21例,母亲5例,河南省新生儿PCD患病率为1/34 317.共发现SLC22A5基因突变18种,其中14种为已知致病突变,4种新发变异:c.1484T＞C、c.431T＞C、c.394-1G＞T、c.265-266insGGCTCGCCACC;常见突变c.1400C＞G、c.760C＞T和c.51C＞G等位基因频率最高,分别为42.3％ (22/52)、11.5％(6/52)和7.7％(4/52).对确诊新生儿补充左旋肉碱50～100mg/(kg·d),随访6～56个月,均未出现临床症状,生长发育正常.结论 河南省新生儿PCD患病率为1/34 317.筛查发现PCD患儿均无临床症状.c.1400C＞G可能为河南省PCD患者的热点突变类型,发现了4种新发变异,丰富了SLC22A5基因的突变谱.

abstractsObjective To study the prevalence,clinical and genetic characteristics of primary carnitine deficiency (PCD).Methods From January 2013 to December 2017,720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry.Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed.Dietary guidance and L-carnitine supplementation were provided to the parents.Growth and intelligence development were surveyed during follow-up.Results In total 21 neonates and 6 mothers were diagnosed with PCD,which yielded an incidence of 1 in 34 317.Eighteen SLC22A5 mutations were detected,which included 4 novel mutations,namely c.1484T＞C,c.394-1G＞T,c.431T＞ C and c.265-266insGGCTCGCCACC.Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations.Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations.Common mutations included c.1400C＞G (42.3％),c.760C＞T (11.5％) and c.51C＞G (7.7％).During the 8 ～ 42 month follow-up,neonates with PCD showed no clinical symptoms but normal growth.Blood level of free carnitine was raised in all mothers after the treatment.Conclusion The incidence of neonatal PCD in Henan is 1 in 34 317,with the most common mutation being c.1400C＞G.Above finding has enriched the spectrum of SLC22A5 gene mutations.