Enzymatic evaluation of glutaric acidemia type 1 by an in vitro probe assay of acylcarnitine profiling using fibroblasts and electrospray ionization/tandem mass spectrometry (MS/MS).

Abstract

Glutaric acidemia type 1 (GA1) is usually diagnosed with an accumulation of glutaric acid (GA) or 3-hydroxyglutaric acid by GC/MS. In some cases, however, excretion of GA is low. We investigated enzymatic evaluation of GA1 using fibroblasts and MS/MS. After loading substrates, lysine, 2-aminoadipate (2AA), or GA, in fibroblasts, and incubating for 96 h, glutarylcarnitine (C5DC) levels in the media were measured. A significant increase of C5DC was observed in GA1 patients, irrespective of substrates added. 2AA showed the largest difference between patients and controls (p = 0.0004). Results suggested enzymatic evaluation of GA1 is useful under appropriate culture conditions.

• Authors: Yuichi Mushimoto, Yuki Hasegawa, Hironori Kobayashi, Hong Li, Jamiyan Purevsuren, Isamu Nakamura, Takeshi Taketani, Seiji Fukuda, Seiji Yamaguchi
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 877 Issue 25 Pg. 2648-51 (Sep 01 2009) ISSN: 1873-376X [Electronic] Netherlands
• PMID: 19467937 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• glutarylcarnitine
• Glutaryl-CoA Dehydrogenase
• Carnitine

Topics

• Amino Acid Metabolism, Inborn Errors (diagnosis, enzymology, metabolism)
• Carnitine (analogs & derivatives, analysis, metabolism)
• Cells, Cultured
• Fibroblasts (chemistry, enzymology, metabolism)
• Glutaryl-CoA Dehydrogenase (metabolism)
• Humans
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tandem Mass Spectrometry (methods)