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)

J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Sep 1;877(25):2648-51. doi: 10.1016/j.jchromb.2009.04.043. Epub 2009 May 4.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • glutarylcarnitine
  • Glutaryl-CoA Dehydrogenase
  • Carnitine