Abstract: FR-PO619
C3 Gene Mutation Abnormality Associated with Atypical Hemolytic Uremic Syndrome in a Patient With Polycystic Kidney Disease
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1002 Genetic Diseases of the Kidney: Non-Cystic
Authors
- Jassal, Vineet K., University of Virginia Div. of Nephrology, Charlottesville, Virginia, United States
- Chopra, Tushar, University of Virginia Div. of Nephrology, Charlottesville, Virginia, United States
- Pourafshar, Negiin, University of Virginia Div. of Nephrology, Charlottesville, Virginia, United States
Introduction
Atypical HUS (aHUS) is a disorder involving dysregulation of the serum complement system, resulting in endothelial cell injury and has been effectively treated with blockade of the complement system. The optimal therapy remains unknown, but advances in genetic testing help determine which patients would benefit from complement system blockade. We report a case of an aHUS patient that benefited from genetic testing after being on dialysis.
Case Description
35-year-old female with a past medical history of obesity, gestational hypertension, history of a miscarriage, diabetes mellitus, and polycystic kidney disease presented with diarhea, acute renal failure, and uremic symptoms after eating uncooked meat. Her serum creatinine (sCr) was 11 mg/dL, platelet count 82 k/µL and labs concerning for microangiopathic hemolytic anemia. A kidney biopsy showed severe acute thrombotic angiopathy; extensive endothelial cell injury and prominent fibrinoid necrosis of vascular walls. There were mild chronic changes in the parenchyma including focal glomerulosclerosis, tubular atrophy and interstitial fibrosis. Genetic testing revealed a variant of unknown significance in the C3 gene. She required hemodialysis, and started on eculizumab, along with prednisone and plasmapheresis. A month later, her kidney function improved to be off dialysis and one year later her sCr is stable 3.0 mg/dl with continued use of eculizumab.
Discussion
Our case highlights the difficulty in recognition of mutations of complement cascade that can be trigged to cause thrombotic microangiopathy. We herein, present a case of atypical hemolytic uremic syndrome that is uncommonly associated with C3 gene mutation. Genetic susceptibility to aHUS has been well recognized with mutations in genes involving complement factor I, membrane cofactor protein, and CFH (complement factor H). These mutations affect the binding regions of C3b that interrelate with CFH, CD46, and complement receptor 1, with resultant dysregulation of the alternative complement pathway. Patients with C3 mutations usually progress to severe disease and ESRD within the first year following presentation. Therefore proper diagnosis and management (including the use of eculizumab) in this group of patients would have a great impact on prognosis of their renal disease.