STABLE-ISOTOPE DILUTION ANALYSIS OF D-2-HYDROXYGLUTARIC AND L-2-HYDROXYGLUTARIC ACID - APPLICATION TO THE DETECTION AND PRENATAL-DIAGNOSIS OF D-2-HYDROXYGLUTARIC AND L-2-HYDROXYGLUTARIC ACIDEMIAS
STABLE-ISOTOPE DILUTION ANALYSIS OF D-2-HYDROXYGLUTARIC AND L-2-HYDROXYGLUTARIC ACID - APPLICATION TO THE DETECTION AND PRENATAL-DIAGNOSIS OF D-2-HYDROXYGLUTARIC AND L-2-HYDROXYGLUTARIC ACIDEMIAS
复制标题
DOI：
10.1203/00006450-199309000-00007
复制
发表时间：
1993-09-01
影响因子：
3.6
通讯作者：
JAKOBS, C
中科院分区：
文献类型：
--
作者：
GIBSON, KM;TENBRINK, HJ;JAKOBS, C
建立了测定生理体液中D-和L-2-羟基戊二酸的稳定同位素稀释法。D-和L-2-羟基戊二酸被分离为0-乙酰基-二(D)-2-丁酯。方法以D，L-13，3，4，4-H-2(4)]-2-羟基戊二酸为内标，氨水化学电离，选择离子监测气相色谱-质谱法。13例L-2-羟基戊二酸尿症患者，L-2-羟基戊二酸浓度分别为：尿液，1283+/-676 mmoL/m o l肌酐(332~2742；n=12例)，血浆47+/-13 m ol/m o l/L(27~62；n=8)，脑脊液62+/-30 m ol/m ol/L(34~100 m ol/m ol，n=6)。1例D-2-羟基戊二酸尿症患儿血D-2-羟基戊二酸水平分别为：尿液1565+/-847 mmoL/mol肌酐(729-2668；n=4)，血浆61+/-14mumol/L(46-73；n=3)，脑脊液15和25mumol/L(n=2)。D-和L-2-羟基戊二酸的控制浓度分别为(D：L)：尿液(n=18)，6.0/-3.6 m ol/m o l肌酐(范围2.8~17)：6.0/-5.4(范围1.3~19)，血浆(n=10)，0.7/-0.2 m ol/L(范围0.3~0.9)：0.6/-0.2(范围0.5~1.0)；脑脊液(n=10)，0.1mumol/L(0.07~0.3)：0.7+/-0.6(0.3~2.3)。对10例对照羊水的调查显示：D：L：1.2+/-0.4mumol/L(范围0.6~1.8)：4.0+/-0.7(范围3.1~5.2)，提示在高危家庭中进行产前诊断的可行性。
A stable-isotope dilution assay has been developed for quantitation of D- and L-2-hydroxyglutaric acids in physiologic fluids. D- and L-2-hydroxyglutaric acids are separated as the 0-acetyl-di-(D)-2-butyl esters. The method uses D,L-13,3,4,4-H-2(4)]-2-hydroxyglutaric acid as internal standard with ammonia chemical ionization, selected ion monitoring gas chromatography-mass spectrometry. For 13 patients with L-2-hydroxyglutaric aciduria, the concentrations of L-2-hydroxyglutaric acid were urine, 1283 +/- 676 mmol/mol creatinine (range, 332-2742; n = 12 patients); plasma, 47 +/- 13 mumol/L (range, 27-62; n = 8); cerebrospinal fluid, 62 +/- 30 mumol/L (range, 34-100; n = 6). In a child with D-2-hydroxyglutaric aciduria, the levels of D-2-hydroxyglutaric acid were urine, 1565 +/-847 mmol/mol creatinine (range, 729-2668; n = 4); plasma, 61 +/- 14 mumol/L (range, 46-73; n = 3); cerebrospinal fluid, 15 and 25 mumol/L (n = 2). Control concentrations of D- and L-2-hydroxyglutaric acids were (D:L): urine (n = 18), 6.0 +/- 3.6 mmol/mol creatinine (range, 2.8-17): 6.0 +/- 5.4 (range, 1.3-19); plasma (n = 10), 0.7 +/- 0.2 mumol/L (range, 0.3-0.9): 0.6 +/- 0.2 (range, 0.5-1.0); cerebrospinal fluid (n = 10), 0.1 +/- 0.1 mumol/L (range, 0.07-0.3): 0.7 +/- 0.6 (range, 0.3-2.3). Investigation of control amniotic fluid (n = 10) revealed the following values (D:L): 1.2 +/- 0.4 mumol/L (range, 0.6-1.8): 4.0 +/- 0.7 (range, 3.1-5.2), suggesting the feasibility of prenatal diagnosis in families at risk.