摘要
目的 探讨串联质谱技术检测羊水代谢产物丙酰基肉碱(C3)及C3/乙酰基肉碱(C2)升高在甲基丙二酸血症(MMA)产前诊断中的应用价值。方法 回顾性分析9例行产前MMA基因诊断的孕妇胎儿羊水代谢产物的浓度。收集116例同孕周正常胎儿羊水样本作为对照组,制定本实验室参考区间。取羊水上清液,制成羊水滤纸片,应用串联质谱(MS/MS)非衍生法进行C3、C3/C2检测,应用气相色谱/质谱(GC/MS)进行有机酸分析,采用Sanger法测序进行基因位点验证。结果 对照组0.5%~99.5%参考区间C3:0.066~0.733μmol/L,C3/C2:0.069~0.312。8例C3和C3/C2的浓度值在参考值区间,其中4例基因正常,4例携带1个变异位点,8例出生后表型正常,新生儿疾病筛查正常;1例C3:2.29μmol/L,C3/C2:1.112高于参考值范围,有机酸分析检出甲基丙二酸41.50μmol/mmol.Cr,基因检测变异位点同先证者,家长选择终止妊娠。结论 胎儿羊水串联质谱技术检测C3和C3/C2结果与基因检测结果有较好的一致性,可以作为一种生化辅助检测手段应用于MMA的产前诊断中,能较大程度上提高MMA产前诊断效率。
Objective To explore the application value of acylcarnitine(C3)and C3/acetylcarnitine(C2)elevation in prenatal diag-nosis of methylmalonic acidemia(MMA)by tandem mass spectrometry.Methods The concentration of fetal amniotic fluid metabolites in 9 prenatal MMA gene diagnosis was retrospectively analyzed.116 normal fetal amniotic fluid samples were collected as control groups for normal pregnancy and the reference interval of this laboratory was formulated.The amniotic fluid supernatant was taken and amniotic fluid filter paper was prepared.The C3 and C3/C2 detection was performed using tandem mass spectrometry(MS/MS)non-derived method,and organic acid analysis was performed using gas chromatography/mass spectrometry(GC/MS),and gene loci verification was performed using Sanger meth-od sequencing.Results The reference range for the control group was 0.5%-99.5%C3:0.066-0.733μmol/L,C3/C2:0.069-0.312,with 8 cases of C3 and C3/C2 concentrations within this range.Among these,4 cases had normal genes,4 carried one variant site,and 8 ex-hibited normal phenotypes after birth,with no neonatal diseases detected;1 case showed C3 at 2.29μmol/L and C3/C2 at 1.112,both ex-ceeding the reference value range.Organic acid analysis detected methylmalonic acid 41.50μmol/mmol.Cr,and the variant site matched that of the proband.The parents chose to terminate the pregnancy.ConclusionThe results of C3 and C3/C2 detected by fetal amniotic fluid tandem mass spectrometry were consistent with the results of genetic detection,which could be used as a biochemical auxiliary detection method in prenatal diagnosis of MMA,and could greatly improve the efficiency of prenatal diagnosis of MMA.
作者
董丽萍
季婵婵
李洪俞
牟凯
牛婷婷
DONG Li-ping;JI Chan-chan;LI Hong-yu;MU Kai;NIU Ting-ting(Neonatal Genetic Metabolic Disease Clinic,Zibo Maternal and Child Health Hospital,Zibo,Shandong 255000,China;不详)
出处
《中国妇幼保健》
2025年第16期3045-3049,共5页
Maternal and Child Health Care of China
基金
山东省妇幼保健协会科技创新科研项目(SFYXH-2023W037)。
关键词
甲基丙二酸血症
基因
串联质谱
产前诊断
Methylmalonic acidemia
Gene
Tandem mass spectrometry
Prenatal diagnosis
