Screening for Fabry disease using whole blood spots fails to identify one-third of female carriers

Abstract

Introduction Recently, a method to analyse dried whole blood spots to diagnose Fabry disease (deficiency of the lysosomal enzyme α-Gal A) was described. However given its X-linked inheritance female Fabry patients can exhibit normal α-Gal A activities. This could lead to underestimation in screening females for Fabry disease using this method. Methods α-Gal A activity was measured in dried whole blood spots of 21 females with documented Fabry disease. Results Only 13/21 (67%) had reduced α-Gal A activities, concluding that one-third of female carriers would not be identified during screening. Additional determination of αGlucosidase activity (αGlu) and the construction of an αGal/αGlu ratio did not increase sensitivity of the assay. Conclusion Assays using α-Gal activity for determination of Fabry disease in females have a high false-negative value. Screening for α-Gal A deficiency by means of whole blood spots should not be performed in a females.