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.
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Authors | David Touboul, Sandrine Roy, Dominique P Germain, Arlette Baillet, Françoise Brion, Patrice Prognon, Pierre Chaminade, Olivier Laprévote |
Journal | Analytical and bioanalytical chemistry
(Anal Bioanal Chem)
Vol. 382
Issue 5
Pg. 1209-16
(Jul 2005)
ISSN: 1618-2642 [Print] Germany |
PMID | 15959771
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Glycosphingolipids
- Trihexosylceramides
- digalactosyl ceramide
- globotriaosylceramide
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Topics |
- Adult
- Child
- Fabry Disease
(genetics, urine)
- Female
- Glycosphingolipids
(urine)
- Heterozygote
- Humans
- Male
- Sex Factors
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Tandem Mass Spectrometry
- Time Factors
- Trihexosylceramides
(urine)
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