Prevalence of Fabry disease GLA variants among patients with parapelvic cysts: a Multicenter Italian Cohort Study

Background: Fabry disease is a rare X-linked disorder characterized by the accumulation of sphingolipids in various vital systems, leading to multiple organ damage. As previous data showed the association between Fabry disease and parapelvic cysts, the aim of our work was to evaluate the prevalence of GLA variants in patients with parapelvic cysts. Methods: From November 2022 to September 2024, we conducted a multicenter cohort study on patients referred to 15 Italian Nephrology Units. The prevalence of GLA variants among patients with parapelvic cysts was compared to the prevalence of Fabry disease in newborns and in chronic kidney disease (CKD )patients. Results: Among 306 enrolled patients with parapelvic cysts, we identified seven different variants in the GLA gene in eight patients (4 females, 4 males) (1.3%, 1.3%, respectively): three patients with two different pathogenic variants (2 males, 1 female) (0.65%, 0.32%, respectively), two patients with variants of uncertain significance (VUS) (2 males) (0.65%) and three with benign variants (3 females) (0.98%). The overall prevalence of GLA variants in our population was 2.6%, which is 11-fold higher than in CKD patients not on dialysis (ND) (0.24%), and this difference resulted statistically significant (P <.0001; 11.07, 95%CI: 4.89; 25.06). Our results showed a prevalence of GLA variants 200 times higher compared to Italian newborn screening programs. Conclusion: Our study is the first to analyze the prevalence of GLA variants in patients with parapelvic cysts, showing results that are significantly higher compared to CKD-ND patients and the general population. Parapelvic cyst identification, even before clinical manifestations, is crucial for early Fabry disease diagnosis and treatment.