摘要：Abstract Background Screening for Fabry disease (FD) in high risk populations yields a significant number of individuals with novel, ultra rare genetic variants in the {GLA} gene, largely without classic manifestations of FD. These variants often have significant residual α-galactosidase A activity. The establishment of the pathogenic character of previously unknown or rare variants is challenging but necessary to guide therapeutic decisions. Objectives To present 2 cases of non-classical presentations of {FD} with renal involvement as well as to discuss the importance of high risk population screenings for FD. Results Our patients with non-classical variants were diagnosed through {FD} screenings in dialysis units. However, organ damage was not limited to kidneys, since LVH, vertebrobasilar dolichoectasia and cornea verticillata were also present. Lyso-Gb3 concentrations in plasma were in the pathologic range, compatible with late onset FD. Structural studies and in silico analysis of p.(Cys174Gly) and p.(Arg363His), employing different tools, suggest that enzyme destabilization and possibly aggregation could play a role in organ damage. Conclusions Screening programs for {FD} in high risk populations are important as {FD} is a treatable multisystemic disease which is frequently overlooked in patients who present without classical manifestations.
关键词：Fabry disease; GLA variants; Late onset variants; Lyso-Gb3
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