Abstract: FR-PO0105
Hidden in Plain Sight: Late Diagnosis of Alport Syndrome with APOL1 High-Risk Genotype
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Melchioris, Andrew Max, Rush University Medical Center, Chicago, Illinois, United States
- Rodby, Roger A., Rush University Medical Center, Chicago, Illinois, United States
Introduction
Genetic testing has become an invaluable tool for diagnosing genetic kidney diseases and CKD of unknown origin. We present a unique case of Alport Syndrome via a COL4A4 gene mutation, concurrent with APOL1 high-risk gene variants, diagnosed at age 61.
Case Description
A 61-year-old black male with a past medical history of CKD stage 3b, bilateral sensorineural hearing loss at birth with bilateral cochlear implants, and type 2 diabetes presented for evaluation of CKD.
Laboratory data were notable for a serum creatinine of 1.3-1.6 mg/dL over the past 15 years, with eGFR ranging from 40-50 mL/min/1.73 m2. Urine studies during this time have been unremarkable, with no protein or red blood cells and a microalbumin-to-creatinine ratio of 5 ug/mg. He was on lisinopril and dapagliflozin with well-controlled blood pressure in this period. There was no known family history of kidney disease and no other relatives with deafness.
Due to his congenital deafness and stable CKD, genetic testing was obtained, revealing a COL4A4 heterozygous gene variant coexistent with two high-risk APOL1 genotypes, G1 and G2 (Fig 1). Biopsy was deferred due to stability of CKD without urinary abnormalities and discovery of these genetic anomalies.
Discussion
Alport syndrome is a genetic disorder caused by mutations in Type IV collagen of the α3-5 genes which interrupt normal triple helix formation and can result in renal as well as extra-renal otic and optic dysfunction. While deafness is most commonly seen in α5, it may be present in α4 and may be present without renal involvement, which is suggested by the lack of hematuria and proteinuria in this case. Patients with α3 and α4 mutations have a slower course compared to those with α5 mutations with only about 15% developing end-stage renal disease by age 50. His HTN and slowly progressive CKD are compatible with the coexistence of two APOL1 high-risk genotypes. We propose he had COL4A4 oto-limited Alport syndrome and APOL1-related renal disease. A renal biopsy would clarify this but was not clinically indicated.
This case highlights the importance of considering genetic testing in patients with unexplained CKD and extra-renal manifestations, as it may reveal a diagnosis with avoidance of an invasive biopsy and may have implications for therapy.