Rare Disease Highlight: Alport Syndrome

Alport syndrome (AS) is a rare disease caused by mutations passed down from parents to their children ¹. It is estimated 30,000-60,000 individuals are affected by AS in the United States ². The mutations target a specific type of collagen in the kidneys, ears, and eyes, which impair its normal function of structural support ^1,3. As is primarily characterized by a continuous decline in kidney function, which usually starts with blood in the urine that is only visible using a microscope. The decrease in kidney function is related to the amount of damage in the kidneys and may eventually progress to kidney failure and end-stage kidney disease (ESKD) ¹. Depending on the severity of the disease, patients may also lose hearing in both ears and/or develop eye abnormalities ³. An early diagnosis of AS is crucial due to the lifetime risk of ESKD, and although a standard process is not established to diagnose AS, observing a positive family history of AS, persistent blood in the urine, hearing loss, and/or eye abnormalities should be enough for the physician to consider the possibility of AS ^4,5. Angiotensin-converting enzyme II inhibitors (ACE-I) are the current standard-of-care (SOC), but only delay the decline in kidney function, so many patients will inevitably progress to ESKD ^1,6. Dialysis or kidney transplant are other options for AS patients, but the patient survival is not improved ⁷. Thus, based on the gaps in the SOC, a disease-modifying therapy for individuals with AS remain a significant unmet medical need.

References used

1.           Torra R, Furlano M. New therapeutic options for Alport syndrome. Nephrol Dial Transplant. 2019;34(8):1272-1279.

2.           NORD. Alport Syndrome. NORD. https://rarediseases.org/rare-diseases/alport-syndrome/. Published 2020. Updated 2020. Accessed 06/16, 2020.

3.           Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med. 2003;348(25):2543-2556.

4.           Kashtan CE. Alport Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews(®). Seattle (WA)2019.

5.           Kashtan CE. Alport Syndrome: Achieving Early Diagnosis and Treatment. Am J Kidney Dis. 2021;77(2):272-279.

6.           Gross O, Licht C, Anders HJ, et al. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int. 2012;81(5):494-501.

7.           Temme J, Kramer A, Jager KJ, et al. Outcomes of male patients with Alport syndrome undergoing renal replacement therapy. Clin J Am Soc Nephrol. 2012;7(12):1969-1976.

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