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Abstract: TH-PO0783

Telomere Biology Disorder from TERT Mutation Associated with Atypical Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • McCoy, Cody Garrett, UC Davis Medical Center, Sacramento, California, United States
  • Gupta, Rajib K., UC Davis Medical Center, Sacramento, California, United States
  • Wiegley, Nasim, UC Davis Medical Center, Sacramento, California, United States
Introduction

Dyskeratosis Congenita (DC) is a rare telomere biology disorder, typically presenting with mucocutaneous abnormalities, bone marrow failure, and cancer predisposition. Renal involvement is uncommon, but emerging evidence suggests associations with podocytopathies and glomerular diseases. We present an atypical case of membranous nephropathy (MN) occurring in the setting of DC, highlighting a potential link between telomerase dysfunction and podocyte injury.

Case Description

A 22-year-old woman with a history of pancytopenia presented with anasarca, limiting daily activity. Workup showed normal kidney function, urinalysis with protein and 7 RBCs/HPF, urine protein-to-creatinine ratio >3 g/g, and serum albumin 1.4 g/dL. Kidney biopsy showed MN with minimal capillary wall thickening and fine spikes on light microscopy, diffuse 3+ IgG staining on IF, few scattered segmental subepithelial deposits and diffuse podocyte foot process effacement on EM. Serum and tissue were negative for PLA2R and NELL1, mass spectrometry is pending for antigen identification. She received rituximab 1 g weekly x2 doses. Due to persistent symptoms, tacrolimus was added for 12 months followed by taper and discontinuation after remission of nephrotic syndrome. She underwent a bone marrow biopsy due to pancytopenia, showing hypocellular bone marrow and depleted trilineage hematopoiesis. Genetic testing identified a pathogenic variant of TERT.

Discussion

To our knowledge, this is the first reported case of potential association between atypical MN in a patient with DC due to TERT mutation. This link likely stems from the role of telomere maintenance in podocyte renewal. This case highlights the clinical vigilance necessary to identify renal involvement of rare genetic conditions. Further research is needed into the role of telomere biology disorders in glomerular disease.

Digital Object Identifier (DOI)