Abstract: PUB133
Role of Genetic Testing in the Diagnosis of Alport Syndrome
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Author
- Elharrif, Khalid, Advocate Trinity Hospital, Chicago, Illinois, United States
Introduction
Alport syndrome is an inherited disorder of the glomerular basement membrane caused by mutations in COL4A3, COL4A4, or COL4A5. It presents with hematuria, progressive renal dysfunction, and may include hearing or ocular abnormalities. Diagnosis traditionally relies on kidney biopsy, but findings can be nonspecific in early disease. Genetic testing has become an important diagnostic tool in such cases.
Case Description
A 23-year-old male presented with nephrotic-range proteinuria. Labs showed creatinine 2.49 mg/dL (eGFR 37 mL/min), BUN 51 mg/dL, and urine protein-to-creatinine ratio of 4 g/g. ANA and ANCA were negative, and complement levels were normal. Kidney biopsy revealed diffusely thin glomerular basement membranes (57 nm) without lamellation or basket-weave appearance. Given his age and unexplained renal dysfunction, genetic testing was performed. A pathogenic COL4A5 mutation was identified, confirming X-linked Alport syndrome. The patient was started on renin–angiotensin system blockade and referred for genetic counseling. Follow-up showed stable renal function and improved proteinuria.
Discussion
This case highlights the limitations of kidney biopsy in early or atypical Alport syndrome. Absence of classic ultrastructural changes does not exclude the diagnosis. Genetic testing provides definitive diagnosis, clarifies inheritance patterns, and guides management.
Early identification allows timely initiation of renoprotective therapy and avoids unnecessary immunosuppression. It also enables family screening and counseling. Incorporating genetic testing in young patients with unexplained proteinuria or hematuria improves diagnostic accuracy and clinical outcomes.
Acknowledgment
References:
1-Kashtan CE. Alport Syndrome and Thin Basement Membrane Nephropathy: Diseases Arising from Mutations in Type IV Collagen. Kidney Int. 2021;99(5):1078–1091.
2-Savige J, Ariani F, Mari F, et al. Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Pediatr Nephrol. 2019;34(7):1175–1189.
3-Rheault MN. Genetic testing in Alport syndrome: The new standard of care. Kidney360. 2021;2(6):1001–1003.