Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Ferreira, S (Author) FMUP; Auray Blais, C (Author) Other; Boutin, M (Author) Other; Lavoie, P (Author) Other; José Pedro Nunes (Author) FMUP; Martins, E (Author) FMUP; Garman, S (Author) Other; João Paulo Oliveira (Author) FMUP

Journal

Title: Clinica Chimica Acta

Vol. 447

Pages: 96-104

ISSN: 0009-8981

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 24 Citations

Other information

Authenticus ID: P-00G-CKR

DOI: 10.1016/j.cca.2015.06.003

Abstract (EN): Recent data have shown that lyso-Gb(3), the deacylated derivative of globotriaosylceramide (Gb(3)), is possibly involved in the pathogenesis of Fabry disease (FD) and might be a clinically useful biomarker of its metabolic load. To test this hypothesis, we assayed Gb(3) and lyso-Gb(3) and related analogs in plasma and/or urine samples of 12 clinically well-characterized subjects carrying several different GM variant alleles associated with a wide range of residual alpha-galactosidase A activities. Urinary Gb(3) was measured by HPLC-MS/MS; plasma and urinary lyso-Gb(3) and related analogs were measured by UPLC-MS/MS. Individual profiles of Gb(3) and lyso-Gb(3) and related analogs closely correlated with the phenotypic data for each subject, discerning the classical FD patient from the two patients carrying cardiac variants as well as those from all the others without FD. The lyso-Gb(3) analog at m/z 836 was found at increased levels only in patients manifesting clinically severe heart disease, irrespective of the pathogenicity of the GLA variant they carried. This finding suggests that this lyso-Gb(3) analog might be an earlier biomarker of progressive heart disease, nonspecific of the FD cardiomyopathy. The possibility that urinary Gb(3) is a specific marker of kidney involvement in FD deserves further study.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9