Abstract: PUB190
A Rare Case of Coexisting Fabry Disease and IgAN Progressing to ESRD
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Cajina Aguirre, Carmen Lorena, The University of Kansas Medical Center, Kansas City, Kansas, United States
- Seth, Nirali, Lady Hardinge Medical College, New Delhi, DL, India
- Shah, Urmil Kiran, Rajiv Gandhi Medical College, Thane, MH, India
- Satish, Poorvikha, St John's National Academy of Health Sciences, Bengaluru, KA, India
- Hamdan, Hana, Kansas State University, Manhattan, Kansas, United States
- Tuffaha, Ahmad M., The University of Kansas Medical Center, Kansas City, Kansas, United States
Introduction
Fabry disease (FD) is a relatively rare X-linked lysosomal storage disorder characterised by the accumulation of glycosphingolipids in multiple organs throughout the body. IgA nephropathy (IgAN), one of the most common primary glomerulonephritides, is characterised by the deposition of glomerular IgA immune complexes. The co-occurrence of FD and IgAN is rare and poses diagnostic and therapeutic challenges. We herein report a unique case of biopsy-proven coexisting FD and IgAN progressing to ESRD requiring transplantation.
Case Description
A 38-year-old woman with a history of childhood neuropathic pain, corneal whorling, and a family history of FD (mother and son genetically confirmed) presented in 2017 with declining eGFR (57 mL/min/1.73m2), proteinuria (urine protein/creatinine 3.4), and microscopic hematuria. Genetic testing identified a GLA V199G mutation with reduced α-Galactosidase A activity, confirming the diagnosis of FD. Renal biopsy revealed foamy podocytes, mesangial IgA, C3, kappa, and lambda deposits, and electron microscopy confirmed the presence of mesangial immune deposits and inclusion bodies, consistent with the diagnosis of Fabry nephropathy and IgAN. She was started on biweekly Agalsidase beta at a dose of 1 mg/kg. Over the next four years, she progressed to stage V chronic kidney disease and underwent peritoneal dialysis for 10 months before receiving a deceased donor kidney transplant in August 2022. Post-transplant, she remained stable on a regimen of prednisone, tacrolimus, and mycophenolate, with continued Agalsidase beta. Follow-up in September 2024 showed preserved graft function (Cr 1.03 mg/dL), and no proteinuria.
Discussion
This case illustrates the clinical overlap of rare genetic nephropathies like FD and common renal pathologies like IgAN, complicating timely diagnosis. Kidney biopsy has a crucial role in confirming the presence of Fabry nephropathy and excluding coexisting pathologies, especially in those with unusual presentation. While IgAN is typically immune-mediated, it is unclear if FD can trigger autoantibodies production, indicating potential shared immunologic link. Early recognition, multidisciplinary approach and tailored therapy, including enzyme replacement therapy and renal transplantation, are crucial for optimizing outcomes in these rare and complex nephropathies.