title: Screening for Fabry disease using whole blood spots fails to identify one-third of female carriers.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine / Clinical Haematology, Academic Medical Center F4-224 Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. g.e.Linthorst@amc.uva.nl
authors.forename: Gabor E
authors.initials: GE
authors.lastname: Linthorst
authors.forename: Anouk C
authors.initials: AC
authors.lastname: Vedder
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D016022:Case-Control Studies; D000795:Fabry Disease / Q000097:blood / Q000175:diagnosis*; D005188:False Negative Reactions; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male