Albina Nowak1, Thomas Mechtler2, David C Kasper3, Robert J Desnick4. 1. Department of Internal Medicine, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. Electronic address: albina.nowak@usz.ch. 2. ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: t.mechtler@archimedlife.com. 3. ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: d.kasper@archimedlife.com. 4. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: robert.desnick@mssm.edu.
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±12ng/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±1.0ng/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<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.
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 FDpatients 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±12ng/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±1.0ng/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<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.
Authors: John Marshall; Jennifer B Nietupski; Hyejung Park; James Cao; Dinesh S Bangari; Cristina Silvescu; Terry Wilper; Kristen Randall; Drew Tietz; Bing Wang; Xiaoyou Ying; John P Leonard; Seng H Cheng Journal: Mol Ther Date: 2019-06-04 Impact factor: 11.454
Authors: Gisela G Slaats; Fabian Braun; Martin Hoehne; Laura E Frech; Linda Blomberg; Thomas Benzing; Bernhard Schermer; Markus M Rinschen; Christine E Kurschat Journal: Sci Rep Date: 2018-07-23 Impact factor: 4.379