Correlation of Lyso-Gb3 levels in dried blood spots and sera from patients with classic and Later-Onset Fabry disease.
- Nowak A Department of Internal Medicine, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. Electronic address: albina.nowak@usz.ch.
- Mechtler T ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: t.mechtler@archimedlife.com.
- Kasper DC ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: d.kasper@archimedlife.com.
- Desnick RJ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: robert.desnick@mssm.edu.
- 2017-07-01
Published in:
- Molecular genetics and metabolism. - 2017
Dried blood spots (DBS)
Fabry disease
Lyso-Gb3
α-Galactosidase A
Adult
Aged
Biomarkers
Chromatography, High Pressure Liquid
Chromatography, Liquid
Dried Blood Spot Testing
Fabry Disease
Female
Glycolipids
Heterozygote
Humans
Male
Middle Aged
Mutation
Phenotype
Regression Analysis
Sphingolipids
Tandem Mass Spectrometry
alpha-Galactosidase
English
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.
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1016/j.ymgme.2017.06.006
- PMID 28663131
- Persistent URL
- https://sonar.ch/global/documents/47611
Statistics
Document views: 30
File downloads:
- Full-text: 0