Alport syndrome

Alport syndrome (also known as hereditary nephritis) is a genetic disorder caused by mutations in genes encoding type IV collagen, a critical structural protein found in the basement membranes of the kidneys, inner ear, and eyes. The three genes involved are COL4A3, COL4A4, and COL4A5, which produce the alpha-3, alpha-4, and alpha-5 chains of type IV collagen, respectively. Defects in these proteins lead to progressive deterioration of the glomerular basement membrane in the kidneys, ultimately resulting in kidney failure. The hallmark features of Alport syndrome include progressive kidney disease (manifesting initially as hematuria and proteinuria, advancing to end-stage renal disease), sensorineural hearing loss (typically affecting high-frequency hearing and developing during late childhood or adolescence), and characteristic ocular abnormalities such as anterior lenticonus (a conical protrusion of the lens), dot-and-fleck retinopathy, and posterior polymorphous corneal dystrophy. The severity and rate of progression vary depending on the mode of inheritance and the specific mutation. Males with X-linked Alport syndrome are most severely affected, often reaching end-stage renal disease by their 20s to 30s, while heterozygous females may have a milder course ranging from isolated hematuria to progressive kidney disease. There is currently no cure for Alport syndrome. Treatment focuses on slowing the progression of kidney disease through the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which reduce proteinuria and delay the onset of renal failure. Early initiation of these medications, ideally before the development of significant proteinuria, has been shown to improve renal outcomes. Kidney transplantation is the treatment of choice for patients who progress to end-stage renal disease, though a small percentage of transplant recipients may develop anti-glomerular basement membrane (anti-GBM) nephritis in the graft. Hearing aids are used to manage sensorineural hearing loss, and regular ophthalmologic monitoring is recommended.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Alport syndrome