Testing & 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 has recently become 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
Leukocyte enzyme assays are used to measure α-galactosidase A activity to confirm diagnosis in patients with suspected Fabry disease.
What is DBS?
What is DBS?
Dry Blood Spot testing is an easy way to measure enzyme activity using a filter paper card.