Prenatal diagnosis of methylmalonic acidemia using test of homocysteine and mass spectrometry in amniotic fluid
10.3760/cma.j.issn.1009-9158.2017.11.011
- VernacularTitle:羊水同型半胱氨酸检测与质谱检测联合产前诊断甲基丙二酸血症
- Author:
Ting CHEN
1
;
Lianshu HAN
;
Wenjun JI
;
Feng XU
;
Jun YE
;
Wenjuan QIU
;
Huiwen ZHANG
;
Yu WANG
;
Zhuwen GONG
;
Xuefan GU
Author Information
1. 200092,上海交通大学医学院附属新华医院 上海市儿科医学研究所 内分泌/遗传科
- Keywords:
Amino acid metabolism;
inborn errors;
Prenatal diagnosis;
Amniotic fluid;
Homocysteine;
Chromatography,liquid;
Tandem mass spectrometry;
Gas chromatography-mass spectrometry
- From:
Chinese Journal of Laboratory Medicine
2017;40(11):880-884
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the value of the combination of homocysteine analysis, liquid chromatography tandem mass spectrometry(LC-MS/MS)and gas chromatography mass spectrometry(GC/MS)in the prenatal diagnosis of combined methylmalonic acidemia and homocystinuria(cblC defect)in amniotic fluid.Methods This is a retrospective study of 187 cases of pregnancies that came to our hospital for prenatal diagnosis between 2014/01-2017/03,among which 78 cases′probands were cblC defect patients and 109 cases′probands were not organic academia patients(control group).Amniotic fluid samples from pregnant women were obtained at 16 -24 weeks of gestation.Propionylcarnitine(C3)and acetylcarnitine (C2)were measured by LC-MS/MS, methylmalonic acid and methylcitric acid were analyzed by GC /MS, and homocysteine was determined by fluorescence polarization immunoassay.Some pregnancies received MMACHC gene sequencing with cultured cells from amniotic fluid.Data were analyzed using Mann-Whitney U and Kruskal-Wallis H tests.Results Among those 78 pregnant women whose probands were diagnosed to be cblC defect,24 cases were diagnosed to be cblC defect(positive group)and 54 pregnant women were diagnosed to be negative(negative group).In positive group, levels of homocysteine, C3, C3/C2, methylmalonic acid and methylcitric acid were all significantly higher than their normal reference ranges, negative group and control group(P values are 0.00).Cases that were diagnosed to be cblC defect by MMACHC gene sequencing were all turned out to be positive in the tests of the above metabolites in amniotic fluid.Cases with negative results of the metabolites were all excluded to be cblC defect by gene sequencing. Besides,2 cases of pregnancies were diagnosed to be positive by homocysteine and mass spectrometric analysis while only one mutation were detected by gene sequencing.Conclusions The combination of homocysteine, LC-MS/MS and GC/MS analysis in amniotic fluid turns out to be reliable for prenatal diagnosis of cblC defect,which may further cover the defect of prenatal diagnosis of those pregnancies whose probands′gene mutation is unknown.
