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 correlation
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 diagnosis,
initial phenotypic assignment, and therapeutic monitoring in patients with Fabry disease.
Published in Molecular Genetics and Metabolism
Authors / * corresponding author
*Albina Nowak a, Thomas Mechtler b, David C. Kasper b, Robert J. Desnick c
a Department of Internal Medicine, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland
b ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria
c Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA