Diagnostic strategy for suspected cases of Fabry disease

Fabry disease (FD) is a progressive, X-linked inherited lysosomal disorder caused by genetic variants in the α-Galactosidase A gene (GLA). Partial or complete deficiency of the enzyme α-Galactosidase A (α-Gal A) results in a progressive accumulation of lipids with terminal α-Galactosyl residues, primarily globotriaosylceramid (Gb3, GL-3) and its deacylated derivative Lyso-GL-3 (Lyso-Gb3) and leads to organ damage. Early diagnosis is vital to prevent clinical complications. We would like to present data from over 65,000 tested cases (males and females) suspicious of FD where both α-Gal A activity together with Lyso-GL-3 levels were measured, followed by confirmatory genetic testing for over 7000 cases. The aim was to demonstrate the benefit of adding Lyso-GL-3 to primary diagnostic screening to avoid unnecessary genetic testing. The results have shown that determination of the enzyme activity combined with the concentration of Lyso-GL-3 (Lyso-Gb3) in Dried Blood Spots (DBS), substantially improved the diagnostic detection of FD in females compared to using enzyme activity alone. In addition, data from validation of innovative self-sampling device for patient sample collection show correlation to DBS results, and it could be utilized for at-home sample collection to significantly improve patient care during current covid-19 time restrictions.