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