Mass spectrometry combined with gene analysis for prenatal diagnosis of glutaric acidemia type Ⅰ
10.3760/cma.j.issn.0578-1310.2017.07.014
- VernacularTitle: 质谱技术联合基因分析进行戊二酸血症Ⅰ型产前诊断研究
- Author:
Feng HAN
1
;
Lianshu HAN
;
Wenjun JI
;
Ting CHEN
;
Feng XU
;
Yu WANG
;
Jun YE
;
Wenjuan QIU
;
Huiwen ZHANG
;
Yizhi JIANG
;
Chen HOU
;
Xuefan GU
Author Information
1. Department of Pediatric Endocrinologic and Genetic Dseases, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- Publication Type:Clinical Trail
- Keywords:
Prenatal diagnosis;
Tandem mass spectrometry;
Gas chromatography-mass spectrometry;
Genetic testing
- From:
Chinese Journal of Pediatrics
2017;55(7):539-543
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the value of amniotic fluid metabolite detection by mass spectrometry combined with gene mutation analysis in the prenatal diagnosis of glutaric acidemia type Ⅰ (GA-Ⅰ).
Method:From January 2009 to December 2016, Department of Pediatric Endocrinology and Genetic, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine carried out prenatal diagnosis for 24 cases of pregnant women with GA-Ⅰproband. 24 pregnant women without organic acidemia proband for conventional prenatal diagnosis at the same period were used as the control group. The pregnant women of the two groups had the amniocentesis at 16 to 20 weeks of gestation.The levels of glutaryl carnitine (C5DC) and octanoylcarnitine (C8) in amniotic fluid were detected by tandem mass spectrometry, and the levels of glutaric acid was determined by gas chromatography-mass spectrometry. All the amniotic fluid cells underwent GCDH gene testing.
Result:A total of 4 cases of fetuses were diagnosed by gene mutation analysis combined with mass spectrometry detection, the levels of C5DC (1.58(0.89-2.85) μmol/L), C5DC/C8 (19.74(12.40-25.93))and glutaric acid (129.96 (90.09-66.02) mmol/mol Cr) were significantly higher than the upper limit of the reference, of which in one case with the proband only on mutation was detected, and in the amniotic fluid cells also only one mutation was detected, the diagnosis was made according to the significantly increased levels of amniotic fluid C5DC, C5DC/C8 and glutaric acid. Twenty cases of fetuses were identified as non-GA-Ⅰchildren, of whom in 2 cases of proband only one mutation was detected, and also in amniotic fluid cells one mutation was detected, in 2 cases the diagnosis was excluded because the normal levels of C5DC, C5DC/C8 and glutaric acid. There were 2 cases whose levels of C5DC or glutaric acid were slightly higher than the upper limit of the reference, but the diagnosis was excluded according to genetic testing.
Conclusion:Prenatal diagnosis cannot be made by gene analysis when the proband mutation is not clear, and it cannot determine whether the fetus is patient when the mass spectrometry detection of amniotic fluid metabolite is mildly abnormal, while mass spectrometry detection of amniotic fluid C5DC, C5DC/C8 and glutaric acid levels combined with GCDH gene analysis can make up the deficiencies, and make the prenatal diagnosis of GA-Ⅰ more reliably.
