Han F, Han L S, Ji W J, Chen T, Xu F, Wang Y, Ye J, Qiu W J, Zhang H W, Jiang Y Z, Hou C, Gu X F
Department of Pediatric Endocrinologic and Genetic Dseases, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Zhonghua Er Ke Za Zhi. 2017 Jul 2;55(7):539-543. doi: 10.3760/cma.j.issn.0578-1310.2017.07.014.
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). From January 2009 to December 2016, , 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. 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. 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.
探讨质谱检测羊水代谢物联合基因突变分析在Ⅰ型戊二酸血症（GA-Ⅰ）产前诊断中的价值。2009年1月至2016年12月，对24例GA-Ⅰ先证者孕妇进行产前诊断。同期24例无有机酸血症先证者的孕妇行常规产前诊断作为对照组。两组孕妇均于妊娠16至20周行羊膜腔穿刺术。采用串联质谱检测羊水戊二酰肉碱（C5DC）和辛酰肉碱（C8）水平，气相色谱-质谱法测定羊水戊二酸水平。所有羊水细胞均进行GCDH基因检测。基因突变分析联合质谱检测共诊断出4例胎儿，其C5DC水平为1.58（0.89 - 2.85）μmol/L、C5DC/C8为19.74（12.40 - 25.93）、戊二酸为129.96（90.09 - 66.02）mmol/mol Cr，均显著高于参考上限，其中1例先证者仅检测到一个突变，羊水细胞也仅检测到一个突变，根据羊水C5DC及C5DC/C8和戊二酸水平显著升高作出诊断。20例胎儿被鉴定为非GA-Ⅰ患儿，其中2例先证者仅检测到一个突变，羊水细胞也检测到一个突变，2例因C5DC、C5DC/C8和戊二酸水平正常而排除诊断。有2例C5DC或戊二酸水平略高于参考上限，但根据基因检测排除诊断。当先证者突变不明确时，基因分析无法进行产前诊断，羊水代谢物质谱检测轻度异常时不能确定胎儿是否患病，而羊水C5DC、C5DC/C8和戊二酸水平的质谱检测联合GCDH基因分析可弥补不足，使GA-Ⅰ的产前诊断更可靠。
