121例肉碱缺乏症新生儿的生化指标与基因结果分析

Analysis of biochemical indexes and gene results of 121 neonates with carnitine deficiency

目的探讨肉碱缺乏症新生儿的血游离肉碱水平与SLC22A5基因的关系,为更好地指导原发性肉碱缺乏症(PCD)筛查诊治工作提供依据。方法收集2015年7月至2023年6月在合肥市新生儿疾病筛查中心采用串联质谱(MS/MS)筛查游离肉碱(C0)低于本实验室切值(10μmol/L)的121例患儿作为研究对象,采用二代测序(NGS)进行基因检测,分析肉碱水平、基因检测结果及两者关系。结果共检测出SLC22A5基因变异29种118个,大多集中于外显子1、4、8,占所有突变位点的75.42%(89/118)。最常见突变前三位的分别是c.1400C>G、c.51C>G及c.760C>T。121例游离肉碱降低的新生儿中,确诊为PCD的有40例,PCD母亲所生的新生儿有20例,单纯PCD基因携带有19例,42例未检出SLC22A5基因突变。PCD母亲所生新生儿初筛C0值比PCD患儿低,差异有统计学意义(P<0.05)。单纯PCD携带组和未检出突变组初筛和复筛C0值均较PCD患儿组高,差异有统计学意义(P<0.05)。结论c.1400C>G、c.51C>G和c.760C>T可能为合肥地区新生儿SLC22A5基因的热点突变。对于PCD的诊断需要结合基因检测与生化指标综合判断,并排除母源性肉碱缺乏症的可能。

Objective To investigate the relationship between serum free carnitine level and SLC22A5 gene in neonates with carnitine deficiency,and to provide evidence for the screening and diagnosis of primary carnitine deficiency(PCD).Methods From July 2015 to June 2023,121 children with free carnitine(C0)lower than the cut value of our laboratory(10μmol/L)were screened by tandem mass spectrometry(MS/MS)in Hefei Neonatal Disease Screening Center,and gene detection was performed by next-generation sequencing(NGS).The level of carnitine,the results of gene detection and their relationship were analyzed.Results A total of 29 variants of SLC22A5 gene were detected,and 118 variants were mainly concentrated in exons 1,4 and 8,accounting for 75.42% of all mutation sites(89/118).The top three most common mutations were c.1400C>G,c.51C>G and c.760C>T.Among 121 neonates with low free carnitine,40 cases were diagnosed with PCD,20 were born to mothers with PCD,19 cases of non-maternal PCD with SLC22A5 gene,and 42 cases with no SLC22A5 gene mutation.The C0 value of newborn infants with maternal PCD was lower than that of infants with PCD,and the difference was statistically significant(P<0.05).The C0 values of non-maternal PCD carrier group and undetected mutation group were higher than those of PCD children in primary screening and rescreening,and the difference was statistically significant(P<0.05).Conclusion c.1400C>G,c.51C>G and c.760C>T may be hot spot mutations of neonatal SLC22A5 gene in Hefei city.The diagnosis of PCD should be combined with genetic detection and biochemical indexes,and the possibility of maternal carnitine deficiency should be ruled out.