Fabry disease and vascular risk factors: future strategies for patient-based studies and the knockout murine model

Fabry disease is secondary to deficiency of the lysosomal enzyme alpha-galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non-clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.

Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.