石家庄地区新生儿Citrin蛋白缺乏症串联质谱筛查结果分析

doi:10.12280/gjszjk.20200585

摘要/Abstract

摘要：

目的:明确Citrin蛋白缺乏症在石家庄地区活产新生儿中的患病率,进一步分析其致病基因突变情况。方法:采用串联质谱技术对石家庄地区2014年1月—2019年12月出生的160 061例新生儿进行血氨基酸水平检测,对疑似患儿进行基因检测。结果:160 061例新生儿中,筛查阳性患儿20例,经SLC25A13基因检测,确诊1例;另1例患儿筛查阴性,于不足1个月因皮肤黄染加重入院,查血串联质谱,显示瓜氨酸和甲硫氨酸升高,尿有机酸结果示4-羟基苯乳酸及4-羟基苯丙酮酸升高,此例患儿筛查呈现假阴性。Citrin蛋白缺乏症在石家庄地区的患病率为2/160 061。基因确诊的1例患儿为SLC25A13基因复合杂合突变,突变位点分别为c.1021+1G>A、c.851_854delTATG,其中c.1021+1G>A在人类基因突变数据库中未见报道。结论:串联质谱技术应用于新生儿疾病筛查可及早发现Citrin蛋白缺乏症患儿;部分患儿筛查呈现假阴性;Citrin蛋白缺乏症在石家庄地区新生儿中的患病率2/160 061;发现了1种SLC25A13基因新突变位点。

关键词: 新生儿筛查, 尿素循环障碍,先天性, 串联质谱法, 突变, Citrin蛋白缺乏症

Abstract:

Objective: To determine the prevalence of citrin protein deficiency in neonates in Shijiazhuang, and further analyze the mutations of pathogenic genes. Methods: A total of 160 061 newborns in Shijiazhuang from January 2014 to December 2019 were detected for blood amino acid levels by tandem mass spectrometry (MS/MS), and the genetic testing were performed for suspected infants. Results: Among the 160 061 newborns, 20 cases were screened as positive cases, including 1 case confirmed the diagnosis with SLC25A13 gene testing; and 1 case that was false negative in newborn screening. The latter child patient was admitted to the hospital due to yellowish skin aggravated in less than 1 month. The blood tandem mass spectrometry showed that citrulline and methionine were elevated. The results of urine organic acids showed that 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid were both significantly increased. The prevalence of citrin protein deficiency in Shijiazhuang is 2/160 061. The gene testing showed that one case was a compound heterozygous mutation of SLC25A13 gene. The mutation sites were c.1021+1G>A and c.851_854delTATG. There was no report of c.1021+1G>A in the human gene mutation database. Conclusions: The application of tandem mass spectrometry in neonatal disease screening can detect the citrin protein deficiency as early as possible. Some newborn patients may be false negative screening; the gene testing is helpful for the diagnosis of citrin protein deficiency. The prevalence of citrin deficiency in Shijiazhuang area is 2/160 061. In this paper, we reported a novel mutation site of SLC25A13 gene.

Key words: Neonatal screening, Urea cycle disorders,inborn, Tandem mass spectrometry, Mutation, Citrin deficiency

贾立云, 封纪珍, 王熙, 马翠霞, 封露露. 石家庄地区新生儿Citrin蛋白缺乏症串联质谱筛查结果分析[J]. 国际生殖健康/计划生育, 2021, 40(3): 182-184.

JIA Li-yun, FENG Ji-zhen, WANG Xi, MA Cui-xia, FENG Lu-lu. Newborn Screening for Citrin Deficiency by Tandem Mass Spectrometry in Shijiazhuang[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(3): 182-184.

图/表 2

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疾病名称	病例	突变基因	核苷酸改变	氨基酸改变	杂合/纯合	来源
Citrin蛋白缺乏症	1	SLC25A13	c.1021+1G>A^△	splicing	杂合	母亲
			c.851_854delTATG	p.M285Pfs*2	杂合	父亲

疾病名称	病例	突变基因	核苷酸改变	氨基酸改变	杂合/纯合	来源
Citrin蛋白缺乏症	1	SLC25A13	c.1021+1G>A^△	splicing	杂合	母亲
			c.851_854delTATG	p.M285Pfs*2	杂合	父亲