DBS assay in the diagnosis of Fabry disease

Abstract

Fabry disease (FD) is a disorder caused by the functional deficit of ��-galactosidase A. Therefore, one of the diagnostic tests for FD is the study of enzymatic activity. This analysis can be performed on plasma, isolated leukocytes or dried blood spot (DBS). The DBS assay is the most widely used method today because it is reliable, fast, cheap and relatively easy to perform. Since 10 years, in the Research Center on Metabolic Diseases of the IBIM-CNR of Palermo, the DBS assay has been used to evaluate the ��-galactosidase A activity in patients with signs and symptoms referable to FD. The assay was optimized to make it more reliable. In a retrospective study, we analyzed the enzymatic activity in 200 individuals affected by the classic form of FD: 100% of the male patients showed null activity, while only 43% of the female patients showed abnormal values. If we had perfomed the DBS assay as the only diagnostic test, 57% of women would not have received the proper diagnosis. Indeed, it is known that affected females can show normal enzyme activity due to inactivation of the X-chromosome. For this reason, the DBS assay is currently considered the main assay for FD diagnosis in males, while genetic analysis is the most reliable test to confirm the clinical suspicion of FD in women.