Alport syndrome
Alport syndrome (hereditary nephritis) is a genetic type IV collagen disorder causing progressive glomerulonephritis with sensorineural hearing loss and ocular abnormalities, most often X-linked, that progresses to end-stage kidney disease in nearly all affected males. Management is supportive with renin-angiotensin system blockade to slow progression; there is no disease-specific therapy.
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What this article covers
- Overview
A hereditary glomerular disease from defective type IV collagen: Alport syndrome (hereditary nephritis) is a genetic disorder of the α3, α4, and α5 chains of type IV collagen, an integral structural…
- Epidemiology
A recognized cause of hereditary glomerulonephritis identified through family history, genetic testing, or biopsy in patients presenting with unexplained persistent hematuria.
- Risk factors
Family history of kidney failure, hematuria, or unexplained deafness: the single most important risk indicator, given the hereditary basis of the disease.
- Pathophysiology
Structural defect in the type IV collagen network of the GBM: most patients have a mutation in COL4A5 (encoding the α5 chain of type IV collagen), and more than 50% of all Alport syndrome patients…
- Clinical features
Classic presentation is a boy younger than 10 years with gross hematuria following a recent upper respiratory infection, often with a positive family history of kidney failure or hearing loss.
- Differential diagnosis
Thin basement membrane nephropathy (benign familial hematuria): isolated glomerular hematuria with normal blood pressure and usually no significant proteinuria, a uniformly thin GBM (typically <250…
- Diagnosis
First, establish the diagnosis by genetic testing identifying a pathogenic COL4A3, COL4A4, or COL4A5 variant, or by kidney biopsy with electron microscopy showing the basket-weave (lamellar)…
- Management
There is no disease-specific or curative therapy; management is supportive and aimed at slowing progression to ESKD.
- Complications
Progressive kidney failure to ESKD: occurs in virtually all affected males, often between the late teenage years and the fourth decade of life, and in some women, typically after age 50 years.
- Prognosis
Nearly all affected males progress to ESKD, most often between age 16 and 35 years, with the rate of progression fairly consistent within a given family but variable between families depending on the specific mutation.
- Prevention
Genetic counseling for families with a known COL4A3, COL4A4, or COL4A5 mutation before pregnancy, to discuss inheritance risk (X-linked, autosomal recessive, or autosomal dominant depending on the family's variant).
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- Hearing loss
Hearing loss is evaluated with the Weber and Rinne tuning fork tests to sort conductive from sensorineural loss at the bedside, then confirmed with audiometry; treatment ranges from cerumen removal or hearing aids to urgent oral prednisone and otolaryngology referral for sudden sensorineural loss.
- Rapidly progressive glomerulonephritis
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