Abstract: TH-PO0584
Digenic Inheritance in Alport Syndrome: Clinical and Genetic Insights
Session Information
- Monogenic Kidney Diseases: Glomerular
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Rajendran, Jackson, RWJBarnabas Health, Toms River, New Jersey, United States
- Toma, Katherine, Jersey Coast Nephrology & Hypertension Associates, LLC, Brick, New Jersey, United States
Introduction
Alport syndrome is a hereditary nephropathy caused by defects in type IV collagen. Though classically inherited in an X-linked dominant pattern, it can also be inherited as autosomal dominant or autosomal recessive. Here we present a rare case of digenic inheritance of Alport Syndrome in a patient with longstanding proteinuria and microscopic hematuria.
Case Description
A 62 year-old woman referred for evaluation of proteinuria and hematuria. Prior evaluation included an elevated urine microalbumin-creatinine ratio and negative urine cytology. Medical history includes atrial fibrillation, hypertension, pre-diabetes, dyslipidemia, and former tobacco use (40 pack-years). Family history is only notable for microscopic hematuria (mother and maternal grandmother). Her father’s history is unclear (died in his early 60s). There is no history of hearing or vision disturbances. Physical exam revealed a euvolemic female with a BMI of 32.8. Her BP was 125/80 mmHg. Lab and genetic evaluation is summarized in Table 1. She was ultimately biopsied, revealing focal global glomerulosclerosis with glomerulomegaly and rare GBM textural abnormality, consistent with Alport syndrome (Figure 1). She completed genetic counseling and started on ARB therapy.
Discussion
Digenic Alport syndrome arises from pathogenic variants in two type IV collagen genes (COL4A3, COL4A4, or COL4A5), often leads to earlier and more severe renal disease compared to monogenic forms. Standard single-gene testing may miss digenic cases, making multigene panels or exome sequencing crucial. Accurate diagnosis informs prognosis, management, and family/transplant planning. Genetic testing should be considered in older adults with persistent hematuria to guide management and family counseling.
Table 1
| Chemistry | Cr 0.7, Albumin 4.4 |
| Urine | MACR 900 mg/g, 3-10 RBC |
| (+) Serologies | ASO: 235.9 |
| (-) Serologies | ANA, MPO/PR3, C3, C4. dsDNA, PLA2R, GBM, serum IFE |
| NateraTM Renasight | COL4A3, COL4A5 |