title: Fast fingerprinting by MALDI-TOF mass spectrometry of urinary sediment glycosphingolipids in Fabry disease.
abstract: Fabry disease (FD) is an X-linked inborn error of glycosphingolipid (GSL) metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A, which results in high levels in lysosomes and biological fluids of globotriaosylceramide (Gb3) and digalactosylceramide (Ga2), also known as galabiosylceramide. We report here a detailed study of the molecular species of GSLs in urinary samples obtained from hemizygous and heterozygous patients by use of matrix-assisted laser desorption ionisation and tandem mass spectrometry (MALDI-MS-MS). Twenty-two and fifteen molecular species were identified in the globotriaosylceramide and digalabiosylceramide series, respectively. The major sphingoid base was sphingosine (d18:1), and dihydrosphingosine (C18:0) and sphingadienine (d18:2) were also present. The molecular profiles obtained by MALDI-TOF-MS enabled us to show significant differences between GSLs composition for young, adult or atypic hemizygote and heterozygote patients. Thus, MALDI-TOF-MS and MS-MS proved a powerful tool for screening a population of patients with clinical signs suggestive of FD by direct and rapid GSL fingerprinting and identification, and for study of the biological processes occurring in glycosphingolipid accumulation.
authors.affiliation: Laboratoire de Spectrométrie de Masse, Institut de Chimie des Substances Naturelles (ICSN-CNRS), Av. de la Terrasse, 91198, Gif-sur-Yvette Cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Touboul
authors.forename: Sandrine
authors.initials: S
authors.lastname: Roy
authors.forename: Dominique P
authors.initials: DP
authors.lastname: Germain
authors.forename: Arlette
authors.initials: A
authors.lastname: Baillet
authors.forename: Françoise
authors.initials: F
authors.lastname: Brion
authors.forename: Patrice
authors.initials: P
authors.lastname: Prognon
authors.forename: Pierre
authors.initials: P
authors.lastname: Chaminade
authors.forename: Olivier
authors.initials: O
authors.lastname: Laprévote
mesh_terms: D000328:Adult; D002648:Child; D000795:Fabry Disease / Q000235:genetics / Q000652:urine*; D005260:Female; D006028:Glycosphingolipids / Q000652:urine*; D006579:Heterozygote; D006801:Humans; D008297:Male; D012737:Sex Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014281:Trihexosylceramides / Q000652:urine*
chemical_list: D006028:Glycosphingolipids; D014281:Trihexosylceramides; C002673:digalactosyl ceramide; C018549:globotriaosylceramide