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Fast fingerprinting by MALDI–TOF mass spectrometry of urinary sediment glycosphingolipids in Fabry disease

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Abstract

Fabry disease (FD) is an X-linked inborn error of glycosphingolipid (GSL) metabolism, caused by a deficiency of the lysosomal α-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.

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Acknowledgements

D.T. is indebted to the Institut de Chimie des Substances Naturelles (CNRS) for a PhD research fellowship.

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Authors and Affiliations

  1. Laboratoire de Spectrométrie de Masse, Institut de Chimie des Substances Naturelles (ICSN-CNRS), Av. de la Terrasse, 91198, Gif-sur-Yvette Cedex, France

    David Touboul & Olivier Laprévote

  2. Service de Pharmaco-Toxicologie, Hôpital Robert Debré, AP-HP, boulevard Sérurier, 75019, Paris, France

    Sandrine Roy & Françoise Brion

  3. EA 3343 Groupe de Chimie Analytique de Paris-Sud, Faculté de Pharmacie Paris XI, rue J.-B. Clément, 92290, Châtenay-Malabry, France

    Arlette Baillet, Patrice Prognon & Pierre Chaminade

  4. Clinical Genetics Unit, Hôpital Européen Georges Pompidou, AP-HP, rue Leblanc, 75918, Paris cedex 15, France

    Dominique P. Germain

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  1. David Touboul
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  2. Sandrine Roy
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  3. Dominique P. Germain
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  4. Arlette Baillet
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  5. Françoise Brion
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  6. Patrice Prognon
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  7. Pierre Chaminade
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  8. Olivier Laprévote
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Correspondence to Olivier Laprévote.

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Touboul, D., Roy, S., Germain, D.P. et al. Fast fingerprinting by MALDI–TOF mass spectrometry of urinary sediment glycosphingolipids in Fabry disease. Anal Bioanal Chem 382, 1209–1216 (2005). https://doi.org/10.1007/s00216-005-3239-8

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  • DOI: https://doi.org/10.1007/s00216-005-3239-8

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