title: 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.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan. mushiu1@med.shimane-u.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mushimoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Jamiyan
authors.initials: J
authors.lastname: Purevsuren
authors.forename: Isamu
authors.initials: I
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D050770:Glutaryl-CoA Dehydrogenase / Q000378:metabolism; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C053168:glutarylcarnitine; D050770:Glutaryl-CoA Dehydrogenase; D002331:Carnitine