自贡市新生儿短链酰基辅酶A脱氢酶缺乏症筛查及确诊结果分析

Analysis of screening and diagnosis results of newborns with short-chain acyl-CoA dehydrogenase deficiency in Zigong City

目的分析自贡市新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)的患病率,总结患儿的临床特征及基因突变特点。方法选取2018年5月至2021年2月于自贡市妇幼保健院自愿接受遗传代谢病筛查的自贡市新生儿24384名。应用串联质谱技术对新生儿的酰基肉碱水平进行筛查检测,初筛及复查阳性者通过尿有机酸分析及遗传代谢病目标捕获测序明确诊断。结果24384名新生儿中初筛阳性249例,复查阳性15例,确诊SCADD 1例,患病率为1/24384。SCADD患儿临床表现无明显异常,串联质谱检测显示血丁酰基肉碱(C4)、C4与乙酰基肉碱(C2)比值、C4与丙酰基肉碱(C3)比值均增高。尿有机酸检测显示乙基丙二酸增高。家系代谢病基因测序发现患儿存在两种SCAD基因突变,一种为已知突变c.1031A>G(来源于母亲);另一种为未报道的突变c.293A>G(来源于父亲),同时发生了SLC22A5基因c.428C>T突变(来源于父亲)。确诊后患儿每日服用左卡尼汀和维生素B_(2),予饮食指导,随访期间均未出现临床症状,体格及智力发育正常。结论自贡市SCADD患病率高于我国其他地区,早期确诊、早期治疗可有效改善患儿预后。

Objective To analyze the prevalence rate of short-chain acyl-CoA dehydrogenase deficiency(SCADD)in newborns in Zigong City,and to summarize the clinical characteristics and gene mutation characteristics of the newborns with SCADD.Methods A total of 24384 newborns from Zigong City who volunteered for screening of inherited metabolic diseases in Zigong City Maternal and Child Health Hospital during May 2018 and February 2021were selected.Tandem mass spectrometry technology was used to screen and detect the acylcarnitine levels of the newborns,and those who were positive in the initial screening and reexamination were confirmedly diagnosed by urinary organic acid analysis and genetic metabolic disease gene sequencing.Results Of the 24384 newborns,249 were positive at the initial screening,and 15 were positive at the reexamination,and 1 was confirmedly diagnosed withSCADD.The prevalence rate was 1/24384.There were no obvious abnormalities in the clinical manifestations of the newborns with SCADD.The results of tandem mass spectrometry showed that blood butyryl-carnitine(C4),ratio of C4 to acetyl-carnitine(C2),ratio of C4 to propionyl-carnitine(C3)were increased.The results of urine organic acid test showed that the level of ethylmalonic acid was increased.Gene sequencing of family metabolic diseases revealed that the newborns had two SCAD gene mutations in which one was a known mutation c.1031A>G(from the mother),and the other was an unreported mutation c.293A>G(from the father).At the same time,the c.428C>T mutation of SLC22A5 gene(from the father)occurred.After the newborns were diagnosed with SCADD,they took L-carnitine and vitamin B_(2)daily and were given dietary guidance.During the follow-up period,no clinical symptoms appeared in the SCADD newborns,and their physical and intellectual developments were normal.Conclusion The prevalence rate of SCADD in newborns in Zigong City is higher than that in other regions of China.Early diagnosis and early treatmentcan effectively improve the prognosis of the SCADD newborns.