title: Late onset variants in Fabry disease: Results in high risk population screenings in Argentina.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Labgen, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Serebrinsky
authors.affiliation: Nephrology Department, Hospital Zonal General de Agudos Evita, Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Nephrology Department, Centro Médico CIPERCA, Catamarca, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Fernandez
authors.affiliation: Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu, Hokkaido, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Research, Not-for-Profit Organization for the Promotion of Research on Intellectual Property Tokyo, Chiyoda, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, AL, United States.
authors.forename: E
authors.initials: E
authors.lastname: Wallace
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, AL, United States.
authors.forename: D
authors.initials: D
authors.lastname: Warnock
authors.affiliation: Department of Clinical Genetics, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
authors.affiliation: Fundación para el Estudio de las Enfermedades Neurometabólicas (FESEN), Buenos Aires, Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Politei
keywords: Fabry disease; GLA variants; Late onset variants; Lyso-Gb3