Gibson K M, ten Brink H J, Schor D S, Kok R M, Bootsma A H, Hoffmann G F, Jakobs C
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
Pediatr Res. 1993 Sep;34(3):277-80. doi: 10.1203/00006450-199309000-00007.
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 O-acetyl-di-(D)-2-butyl esters. The method uses D,L-[3,3,4,4-2H4]-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.
已开发出一种稳定同位素稀释分析法，用于定量生理体液中的D-和L-2-羟基戊二酸。D-和L-2-羟基戊二酸以O-乙酰基-二-(D)-2-丁酯形式分离。该方法使用D,L-[3,3,4,4-2H4]-2-羟基戊二酸作为内标，采用氨化学电离、选择离子监测气相色谱-质谱法。对于13例L-2-羟基戊二酸尿症患者，L-2-羟基戊二酸的浓度为：尿液，1283±676 mmol/mol肌酐（范围332 - 2742；n = 12例患者）；血浆，47±13 μmol/L（范围27 - 62；n = 8）；脑脊液，62±30 μmol/L（范围34 - 100；n = 6）。在1例D-2-羟基戊二酸尿症患儿中，D-2-羟基戊二酸的水平为：尿液，1565±847 mmol/mol肌酐（范围729 - 2668；n = 4）；血浆，61±14 μmol/L（范围46 - 73；n = 3）；脑脊液，15和25 μmol/L（n = 2）。D-和L-2-羟基戊二酸的对照浓度为（D:L）：尿液（n = 18），6.0±3.6 mmol/mol肌酐（范围2.8 - 17）：6.0±5.4（范围1.3 - 19）；血浆（n = 10），0.7±0.2 μmol/L（范围0.3 - 0.9）：0.6±0.2（范围0.5 - 1.0）；脑脊液（n = 10），0.1±0.1 μmol/L（范围0.07 - 0.3）：0.7±0.6（范围0.3 - 2.3）。对10例对照羊水的研究得出以下值（D:L）：1.2±0.4 μmol/L（范围0.6 - 1.8）：4.0±0.7（范围3.1 - 5.2），提示在有风险的家庭中进行产前诊断的可行性。
