Testing and Screening

Definitive diagnosis of Fabry disease in males requires biochemical testing to confirm absent or deficient α-galactosidase A activity.

The standard laboratory test is measurement of enzyme activity in leukocytes.1 Enzyme activity can also be measured in plasma but this method is less sensitive and should always be confirmed with a leukocyte assay.2

Dried blood spot (DBS) testing is available for Fabry disease and has made screening more feasible while demonstrating increased sensitivity and specificity compared to previous leukocyte assays.3

Biochemical testing is not routinely used to confirm diagnosis in females as female heterozygotes express variable levels of α-galactosidase A activity that may fall within the normal range.4 However, locally the National Referral Laboratory has demonstrated increased sensitivity using DBS testing in females and therefore this can be used as a screening test.3 There is no correlation between levels of α-galactosidase A activity and severity of disease or rate of progression in heterozygous women.5

Molecular analysis to confirm the presence of a disease-causing GLA gene mutation is required to confirm diagnosis in females, even in patients with a negative DBS result. The lower sensitivity of DBS testing in females compared with males is a consequence of random X-inactivation resulting normal α-galactosidase A activity levels in a proportion of female heterozygotes with Fabry disease. It does not reflect a problem with the test itself.6


  1. 1.Germain DP. (2010) Fabry disease. Orphanet J Rare Dis 5: 30.
  2. 2.Hoffmann B, Beck M, Sunder-Plassmann G, et al. (2007) Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapy--a retrospective analysis from the Fabry Outcome Survey. Clin J Pain 23(6): 535-542.
  3. 3.Stark S, Fong B, Fletcher J, Fietz M, editors. Screening For Fabry Disease Using Dried Blood Spots. 38th Human Genetics Society of Australasia Annual Scientific Meeting; 2014 August 3-6; Adelaide, South Australia.
  1. 4.Linthorst GE, Vedder AC, Aerts JM, Hollak CE. (2005) Screening for Fabry disease using whole blood spots fails to identify one-third of female carriers. Clin Chim Acta 353(1-2): 201-203. 5. Wang RY, Lelis A, Mirocha J, Wilcox WR. (2007) Heterozygous Fabry
  2. 5.Wang RY, Lelis A, Mirocha J, Wilcox WR. (2007) Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med 9(1): 34-45.
  3. 6.Ceci R, de Francesco PN, Mucci JM, Cancelarich LN, Fossati CA, Rozenfeld PA. (2011) Reliability of enzyme assays in dried blood spots for diagnosis of 4 lysosomal storage disorders. Advances in Biological Chemistry 1: 58-64.