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ENGLISH ABSTRACT
质谱技术检测羊水代谢物对丙酸血症进行产前诊断
韩凤
鄂慧姝
韩连书
季文君
徐烽
叶军
邱文娟
张惠文
顾学范
作者及单位信息
·
DOI： 10.3760/cma.j.issn.2096-2916.2017.11.011
Prenatal diagnosis of propionic acidemia by amniotic fluid metabolites analysis using mass spectrometry
Han Feng
E Huishu
Han Lianshu
Ji Wenjun
Xu Feng
Ye Jun
Qiu Wenjuan
Zhang Huiwen
Gu Xuefan
Authors Info & Affiliations
Han Feng
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
E Huishu
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Han Lianshu
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Ji Wenjun
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Xu Feng
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Ye Jun
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Qiu Wenjuan
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zhang Huiwen
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Gu Xuefan
Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
·
DOI： 10.3760/cma.j.issn.2096-2916.2017.11.011
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摘要

目的探讨串联质谱及气相色谱质谱技术检测羊水中的酰基肉碱及有机酸用于丙酸血症(propionic acidemia, PA)产前诊断的诊断价值。

方法收集2010年—2016年40例于上海交通大学医学院附属新华医院进行产前诊断且生育过PA患儿的孕妇作为PA母亲组。从同期进行常规产前诊断孕妇中随机选取40例作为对照组。2组孕妇均于妊娠16~20周进行羊膜腔穿刺术抽取羊水。采用串联质谱检测羊水丙酰肉碱(propionylcarnitine, C3)、乙酰肉碱(acetylcarnitine, C2)水平,采用气相色谱质谱检测羊水甲基枸橼酸、3-羟基丙酸水平,部分羊水细胞进行基因检测。

结果PA母亲组4例孕妇羊水C3[9.53(6.06~11.45)mmol/L]、C3/C2[1.03(0.62~1.43)]、甲基枸橼酸[3.15(2.05~4.58) mmol/mol肌酐]水平均高于对照组[1.14(0.52~ 3.40)mmol/L, 0.11(0.05~0.22), 0.00(0.00~0.34) mmol/mol肌酐],提示胎儿为PA阳性患儿,检出率为10%;其中3例进行了基因突变检测均检测到突变位点。3-羟基丙酸在对照组与阳性组之间差异无统计学意义。

结论PA孕妇再生PA患儿的几率为10%左右,可利用串联质谱及气相色谱质谱技术检测羊水中的C3、甲基枸橼酸水平,对先证者为PA的孕妇进行产前诊断。

串联质谱;气相色谱质谱;产前诊断;丙酸血症(PA)
ABSTRACT

ObjectiveTo investigate the value of acylcarnitine and organic acid in amniotic fluid for the diagnosis of propionic acidemia (PA) by tandem mass spectrometry and gas chromatography-mass spectrometry (GC-MS).

MethodsFrom 2010 to 2016, 40 pregnant women with PA neonate received pregnatal diagnosis of PA in Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (as PA mother group). Another 40 cases of pregnant women for conventional prenatal diagnosis at the same period were collected as control group. The pregnant women of two groups had the amniocentesis at 16-20 weeks of gestation. The levels of propionylcarnitine (C3) and acetylcarnitine (C2) in amniotic fluid were detected by tandem mass spectrometry, and the levels of methylcitrate acid and 3-hydroxypropionate were determined by gas chromatography-mass spectrometry. Part of the amniotic fluid cells were made genetic testing.

ResultsIn PA mother group, 4 fetuses were positive and the detection rate was 10%. The levels of C3 [9.53 (6.06-11.45)mmol/L], C3/C2 [1.03 (0.62-1.43)] and methylcitrate acid [3.15 (2.05-4.58) mmol/molCr] in amniotic fluid of these 4 cases were higher than those in control group[1.14 (0.52~3.40) mmol/L, 0.11 (0.05-0.22), 0.00 (0.00-0.34)mmol/molCr]. Three cases of the PA-positive children were diagnosed by gene testing. There was no significant difference of 3-hydroxypropionic acid between control group and the positive group.

ConclusionFor pregnant women with PA proband, the probability of children regeneration with PA is about 10%. Tandem mass spectrometry and gas chromatography-mass spectrometry can be used to detect the levels of C3 and methylcitrate in amniotic fluid, and to make prenatal diagnosis of PA.

Tandem mass spectrometry;Gas chromatography-mass spectrometry;Prenatal diagnosis;Propionic acidemia (PA)
Han Lianshu, Tel: +86-13818170919, Email: nc.defmoabc.361demauhnixslnuhsnailnah
The National Key Research and Development Program of China (2016YFC0901505)
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引用本文

韩凤,鄂慧姝,韩连书,等. 质谱技术检测羊水代谢物对丙酸血症进行产前诊断[J]. 中华生殖与避孕杂志,2017,37(11)：918-922.

DOI:10.3760/cma.j.issn.2096-2916.2017.11.011

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丙酸血症(propionic acidemia, PA)是由于丙酰CoA羧化酶(propionyl-CoA carboxylase, PCC)活性缺乏, 导致支链氨基酸和偶数链脂肪酸代谢异常的一种较常见的有机酸血症, 为常染色体隐性遗传病 [ 1 , 2 ]。PCC是由α和β两个亚基共同组成的异聚体, 编码α和β亚基的基因分别为PCCA和PCCB, 任意一个致病基因发生突变均会导致正常代谢途径受阻, 旁路代谢途径激活, 大量代谢产物如丙酸、3-羟基丙酸、甲基枸橼酸等堆积, 引起一系列生化异常及多脏器损害。PA患儿临床表现以神经系统症状为主, 大多数患儿即使接受治疗, 后期也会遗留神经系统损伤, 预后较差 [ 3 , 4 ]。因此, 有必要对再次妊娠的PA患儿母亲进行产前诊断, 避免再次生育PA患儿。产前诊断方法包括绒毛膜组织、羊水细胞酶活性和基因突变分析, 羊水代谢物直接检测, 其中近几年快速发展的质谱技术通过检测羊水中酰基肉碱及甲基枸橼酸含量, 为产前诊断提供了快速、准确的方法 [ 5 ]。国外已有利用气相色谱质谱技术检测羊水有机酸水平诊断PA的报道, 本研究利用串联质谱及气相色谱质谱对就诊于上海交通大学医学院附属新华医院的40例孕妇进行了PA产前诊断, 现结果报道如下。
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备注信息
A
韩连书, Tel: +86-13818170919, Email: nc.defmoabc.361demauhnixslnuhsnailnah
B
国家重点研发计划 (2016YFC0901505)
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