Fabry disease: perspectives of urinary proteomics.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the lysosomal enzyme a-galactosidase A (a-GalA). The resulting deficiency in a-GalA activity leads to intra-lysosomal accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organ systems. As a consequence, a multisystem disorder develops, culminating in strokes and progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though monitoring treatment is hampered by a lack of surrogate markers of response. Furthermore, even if signs and symptoms of the disease become manifest in childhood, its diagnosis is often delayed. Biomarkers that predict disease progression and respond relatively quickly to effective therapy may be useful to follow individual patients or groups of patients. Here we report the use of 2 different mass spectrometry-based proteomic techniques to identify disease-associated compositional changes that can be used as early biomarkers of the pathology, as well as for monitoring the effectiveness of ERT. To this purpose, we compared the renal Fabry urinary proteome with normal (control) urine using, respectively, 2-dimensional gel electrophoresis and label-free quantification. Our preliminary results show that the urinary protein pattern of affected patients can be easily distinguished from that of healthy subjects both qualitatively and quantitatively, thus encouraging further studies in the search for FD-specific biomarkers using this proteomic approach.