Abstract
Background/Objectives: Fabry disease (FD) is a genetic lysosomal storage disease caused by a pathogenic variant in GLA gene coding for a functional alpha-galactosidase A enzyme whose disfunction leads to globotriaosylceramide (Gb3) accumulation in cells, which results in multiple organ disorders. The aim of this study was to identify mutations associated with Fabry disease among 829 kidney transplant recipients and to investigate the correlation between the factors such as age, dialysis vintage, eGFR, proteinuria and corticosteroid dose and the deviations in alpha-galactosidase A and lyso-Gb3 levels. Methods: Dry blood spot samples were collected for genetic analysis. The GLA genetic variants were analysed by an amplicon-based next-generation sequencing approach in all female patients and in male patients with reduced alpha-galactosidase A levels. Alpha-galactosidase A and Lyso-Gb3 were not determined in female patients. Pearson's correlation coefficient was used to assess the relationship between the above-mentioned factors with the activity of alpha-galactosidase A and Lyso-Gb3. Results: Genetic testing was performed in 476 patients, all female patients (334), 69 male patients with decreased level of alpha-galactosidase A activity, one male patient with alpha-galactosidase A levels above the quantification limit and 72 male patients with no interpretable results of alpha-galactosidase A activity due to preanalytical error. In 3 (0.4%) male patients, hemizygous mutations associated with Fabry disease were found, and those were c.427G>A p.(Ala143Thr), c.1181T>C p.(Leu394Pro), and c.352C>T p.(Arg118Cys). The dose of corticosteroid therapy seemed to be positively correlated to alpha-galactosidase A activity and negatively to Lyso-Gb3 levels in blood. Conclusions: Genetic testing of individuals with chronic kidney disease and reporting of genetic variants associated with the Fabry phenotype are important to improve the overall knowledge of the disease. Further research is needed to define factors influencing levels of alpha-galactosidase A and Lyso-Gb3.