Abstract: PUB279
Coexistence of Alport Syndrome and Autosomal Dominant Polycystic Kidney Disease: A Case Report
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Ibrahim, Abdelrahman, University of Utah Health, Salt Lake City, Utah, United States
- Altawallbeh, Zena, University of Utah Health, Salt Lake City, Utah, United States
- Al-Rabadi, Laith, University of Utah Health, Salt Lake City, Utah, United States
Background
Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Alport Syndrome (AS) are genetic kidney disorders, which affect individuals in different ways. ADPKD, which usually appears in adulthood, is marked by multiple fluid-filled cysts in the kidneys. However, ADPKD can also be diagnosed early in life, when based on family history, with advanced imaging such as MRI. Meanwhile, AS affects renal glomeruli, the inner ears and eyes. Histologically, AS shows segmental thinning and thickening of the glomerular basement membrane (GBM), which can occur just with the thinning of the GBM in an early stage of the disease. Both of these conditions lead to end-stage renal disease (ESRD). While ADPKD arises from gene mutations influencing kidney development and function, AS is linked to mutations in collagen genes essential for kidney structure and function.
We present a case of a 34-year-old woman with early-onset ADPKD, exhibiting proteinuria of 1.5 grams, which is atypical for ADPKD, that has subsequently resolved. Additionally, she reported hearing loss. Along with a subsequent biopsy, genetic testing identified an autosomal recessive AS gene mutation. Patient’s functions are stable, with normal creatinine and glomerular filtration rates. Maternal ADPKD history with renal failure requiring transplantation is noted, but two siblings also are asymptomatic.
Methods
Genetic analysis was conducted with next-generation sequencing (NGS), in conjunction with copy
number variation (CNV) analysis. Mutations were confirmed through polymerase chain reaction (PCR) and Sanger sequencing. Renal ultrasound and biopsy were carried out, and audiological and ophthalmological examinations were ordered.
Results
Genetic analysis revealed a pathogenic deletion in COL4A3 c.4265-4273 del (p.Ser1422_Gly1424del), as well as a pathogenic mutation in PKD1 gene, consistent with ADPKD. Renal ultrasound showed enlarged kidneys, consistent with polycystic kidney disease while renal biopsy indicated borderline-thin GBM.
Conclusion
This case emphasizes an extremely rare concurrence of AS and ADPKD, underscoring the importance of considering the factor of overlapping inherited kidney diseases. Therefore, comprehensive genetic and familial evaluations in such cases should be requested for accurate diagnosis and management, particularly in cases with atypical overlapping disease symptoms.