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Correlation of Lyso-Gb3 levels in dried blood spots and sera from patients with classic and Later-Onset Fabry disease


Nowak, Albina; Mechtler, Thomas; Kasper, David C; Desnick, Robert J (2017). Correlation of Lyso-Gb3 levels in dried blood spots and sera from patients with classic and Later-Onset Fabry disease. Molecular Genetics and Metabolism, 121(4):320-324.

Abstract

Background: Fabry disease (FD), an X-linked lysosomal storage disorder, results from the deficient activity of α-galactosidase A (α-Gal A) and the accumulation of its substrates, globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Here, we compared the levels of Lyso-Gb3 in dried blood spots (DBS) and sera in affected males and heterozygotes with the “Classic” and “Later-Onset” phenotypes. Methods: The Lyso-Gb3 concentrations in DBS and sera from 56 FD patients were determined by highly sensitive electrospray ionization liquid chromatography tandem mass spectrometry.
Results: The serum Lyso-Gb3 levels in 18 and 5 affected males with the Classic and Later-Onset phenotypes, were 61 ± 38 and 14 ± 12 ng/mL, respectively. Lyso-Gb3 levels in 30 females from Classic families and three females from Later-Onset families were 10 ± 5.4 and 2.4 ± 1.0 ng/mL, respectively. The linear regression model with serum Lyso-Gb3 as the dependent variable and DBS Lyso-Gb3 an independent variable was described by the function y = −1.83 + 1.68 ∗ x and showed a high coefficient of determination, R2 = 0.976. The overall correla-tion between the Lyso-Gb3 levels in DBS and sera was high (R = 0.99; p b 0.001).
Conclusion: DBS provides a convenient, sensitive, and reproducible source to measure Lyso-Gb3 levels for diagno-sis, initial phenotypic assignment, and therapeutic monitoring in patients with Fabry disease.

Abstract

Background: Fabry disease (FD), an X-linked lysosomal storage disorder, results from the deficient activity of α-galactosidase A (α-Gal A) and the accumulation of its substrates, globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Here, we compared the levels of Lyso-Gb3 in dried blood spots (DBS) and sera in affected males and heterozygotes with the “Classic” and “Later-Onset” phenotypes. Methods: The Lyso-Gb3 concentrations in DBS and sera from 56 FD patients were determined by highly sensitive electrospray ionization liquid chromatography tandem mass spectrometry.
Results: The serum Lyso-Gb3 levels in 18 and 5 affected males with the Classic and Later-Onset phenotypes, were 61 ± 38 and 14 ± 12 ng/mL, respectively. Lyso-Gb3 levels in 30 females from Classic families and three females from Later-Onset families were 10 ± 5.4 and 2.4 ± 1.0 ng/mL, respectively. The linear regression model with serum Lyso-Gb3 as the dependent variable and DBS Lyso-Gb3 an independent variable was described by the function y = −1.83 + 1.68 ∗ x and showed a high coefficient of determination, R2 = 0.976. The overall correla-tion between the Lyso-Gb3 levels in DBS and sera was high (R = 0.99; p b 0.001).
Conclusion: DBS provides a convenient, sensitive, and reproducible source to measure Lyso-Gb3 levels for diagno-sis, initial phenotypic assignment, and therapeutic monitoring in patients with Fabry disease.

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Contributors:ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2017
Deposited On:19 Oct 2017 10:09
Last Modified:17 Jun 2018 00:00
Publisher:Elsevier
ISSN:1096-7192
OA Status:Green
Publisher DOI:https://doi.org/10.1016/j.ymgme.2017.06.006

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