Diagnosis of glutaric aciduria type 1 by measuring 3-hydroxyglutaric acid in dried urine spots by liquid chromatography tandem mass spectrometry

• Verfasst von: Al-Dirbashi, Osama Y. [VerfasserIn]
• Verfasst von: Kölker, Stefan [VerfasserIn]
• Verfasst von: Ng, Dione [VerfasserIn]
• Verfasst von: Fisher, Lawrence [VerfasserIn]
• Verfasst von: Rupar, Tony [VerfasserIn]
• Verfasst von: Lepage, Nathalie [VerfasserIn]
• Verfasst von: Rashed, Mohamed S. [VerfasserIn]
• Verfasst von: Santa, Tomofumi [VerfasserIn]
• Verfasst von: Goodman, Stephen I. [VerfasserIn]
• Verfasst von: Geraghty, Michael T. [VerfasserIn]
• Verfasst von: Zschocke, Johannes [VerfasserIn]
• Verfasst von: Christensen, Ernst [VerfasserIn]
• Verfasst von: Hoffmann, Georg F. [VerfasserIn]
• Verfasst von: Chakraborty, Pranesh [VerfasserIn]
• Titel: Diagnosis of glutaric aciduria type 1 by measuring 3-hydroxyglutaric acid in dried urine spots by liquid chromatography tandem mass spectrometry
• Verf.angabe: Osama Y. Al-Dirbashi, Stefan Kölker, Dione Ng, Lawrence Fisher, Tony Rupar, Nathalie Lepage, Mohamed S. Rashed, Tomofumi Santa, Stephen I. Goodman, Michael T. Geraghty, Johannes Zschocke, Ernst Christensen, Georg F. Hoffmann, Pranesh Chakraborty
• Jahr: 2011
• Umfang: 8 S.
• Fussnoten: First published: 27 October 2010 ; Gesehen am 28.02.2022
• Titel Quelle: Enthalten in: Journal of inherited metabolic disease
• Ort Quelle: Hoboken, NJ : Wiley, 1978
• Jahr Quelle: 2011
• Band/Heft Quelle: 34(2011), 1, Seite 173-180
• ISSN Quelle: 1573-2665
• DOI: doi:10.1007/s10545-010-9223-2
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1794046097

Abstract

Accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3HGA) in body fluids is the biochemical hallmark of type 1 glutaric aciduria (GA1), a disorder characterized by acute striatal degeneration and a subsequent dystonia. To date, methods for quantification of 3HGA are mainly based on stable isotope dilution gas chromatography mass spectrometry (GC-MS) and require extensive sample preparation. Here we describe a simple liquid chromatography tandem MS (LC-MS/MS) method to quantify this important metabolite in dried urine spots (DUS). This method is based on derivatization with 4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole (DAABD-AE). Derivatization was adopted to improve the chromatographic and mass spectrometric properties of the studied analytes. Derivatization was performed directly on a 3.2-mm disc of DUS as a sample without extraction. Sample mixture was heated at 60°C for 45 min, and 5 μl of the reaction solution was analyzed by LC-MS/MS. Reference ranges obtained were in excellent agreement with the literature. The method was applied retrospectively for the analysis of DUS samples from established low- and high-excreter GA1 patients as well as controls (n = 100). Comparison of results obtained versus those obtained by GC-MS was satisfactory (n = 14). In populations with a high risk of GA1, this approach will be useful as a primary screening method for high- or low-excreter variants. In these populations, however, DUS analysis should not be implemented before completing a parallel comparative study with the standard screening method (i.e., molecular testing). In addition, follow-up DUS GA and 3HGA testing of babies with elevated dried blood spot C5DC acylcarnitines will be useful as a first-tier diagnostic test, thus reducing the number of cases requiring enzymatic and molecular analyses to establish or refute the diagnosis of GA1.