Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular accumulation of glycosphingolipids in many tissues and fluids, including the kidneys. We report a single family with Fabry disease that includes seven patients carrying the pathogenic variant c.797A>C in the GLA gene, with remarkable variability in kidney involvement, assessed based on clinical, biological, and histological data. The patients were monitored for 2–9 years, and all received enzyme replacement therapy. Kidney involvement was variable and included severely decreased GFR with significant proteinuria, mildly to moderately decreased GFR with proteinuria, mildly decreased GFR with microalbuminuria or normoalbuminuria, hyperfiltration with normoalbuminuria, and preserved kidney function. All patients who underwent kidney biopsy presented with Fabry-specific lesions and, in some cases, chronic histological damage. This study provides valuable insights into kidney involvement evaluated through kidney biopsy, personalized management strategies for family members according to their phenotype, and long-term follow-up of kidney function. We underscore the importance of molecular screening of the GLA gene in all family members for early identification of the disease and early initiation of specific treatments that can prevent or delay the progression of this disease.

Fabry disease (FD) is a rare, X-linked, lysosomal storage multisystemic disorder which may lead to kidney failure and require kidney transplantation (KT). Data on long-term kidney allograft outcomes and the evolution of systemic FD under dis-ease-specific therapy after KT remain limited. We retrospectively evaluated six kidney transplant recipients (KTRs) with FD followed in our center for median tine after KT of 7 years (range, 4-13). Five patients (83.3%) were males and five had a classic Fabry phe-notype. At last follow-up patient survival was 100% and five out of six KTR had a func-tional kidney graft. Among KTRs with a functioning graft, the median change is esti-mated glomerular filtration rate from 1-year to last follow-up was +3.3 ml/min/1.73m2 (range, -50.7 to +10.5), while proteinuria remained low. One patient developed late an-tibody-mediated rejection with de novo donor-specific antibodies and graft loss at 8 years post-transplantation. Five KTRs were receiving enzyme replacement therapy at the time of KT. Three patients were subsequently switched to migalastat and two later returned to enzyme replacement therapy. Lyso-Gb3 and cardiac structural parameters showed heterogenous longitudinal trajectories despite generally preserved kidney graft function. No cardiovascular events occurred during follow-up. These findings support KT as an effective renal replacement therapy in FD and highlight the need for contin-uous Fabry-specific therapy and multidisciplinary surveillance after transplantation.

Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular ac-cumulation of glycosphingolipids in many tissues and fluids, including the kidney. We report a single family with Fabry disease that includes 7 patients carrying the path-ogenic variant c.797A>C in the GLA gene, with remarkable variability of kidney in-volvement, assessed based on the clinical, biological and histological data. The patients were monitored for a period of 2–9 years, and all of them received enzyme replacement therapy. This study provides valuable insights into kidney involvement evaluated through kidney biopsy, personalized management strategies for family members ac-cording with their phenotype, and long-term follow-up of the kidney function. We un-derscore the importance of molecular screening of the GLA gene in all family members for early identification of the disease and early initiation of specific treatment that can potentially prevent or delay the progression of the disease.