Abstract
ABSTRACT: 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-(o)-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 μmol/L (range, 27–62; n = 8); cerebrospinal fluid, 62 ± 30 μmol/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 μmol/L (range, 46–73; n = 3); cerebrospinal fluid, 15 and 25 μmol/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 μmol/L (range, 0.3− −0.9): 0.6 ± 0.2 (range, 0.5–1.0); cerebrospinal fluid (n = 10), 0.1 ± 0.1 μmol/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 μmol/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.
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Gibson, K., Ten Brink, H., Schor, D. et al. Stable-Isotope Dilution Analysis of D- and L-2-Hydroxyglutaric Acid: Application to the Detection and Prenatal Diagnosis of D- and L-2-Hydroxyglutaric Acidemias. Pediatr Res 34, 277–280 (1993). https://doi.org/10.1203/00006450-199309000-00007
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DOI: https://doi.org/10.1203/00006450-199309000-00007
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