Alport

Alport syndrome is a hereditary kidney disease marked by progressive nephritis and extras renal features such as sensorineural hearing loss and ocular abnormalities. It results from mutations in type IV collagen genes, affecting basement membranes in the kidney, inner ear, and eye.

Genetics: The disease occurs in several forms. The most common is X-linked, due to COL4A5 mutations. Autosomal recessive disease arises from biallelic COL4A3 or COL4A4 mutations, and autosomal dominant forms are rare.

Pathophysiology: Defective type IV collagen weakens basement membranes, producing thinning and splitting of the glomerular basement membrane (GBM). Electron microscopy often shows a basket-weave GBM pattern.

Clinical features: Hematuria typically appears in childhood, with proteinuria that may progress to renal failure. Sensorineural hearing loss usually develops in adolescence or early adulthood. Eye findings can include anterior lenticonus and dot-and-fleck retinopathy.

Diagnosis: Diagnosis rests on clinical features, family history, and genetic testing. Renal biopsy may show GBM abnormalities and loss of specific collagen chains; electron microscopy and immunohistochemistry can aid confirmation.

Management and prognosis: There is no cure. Treatment aims to delay kidney failure, typically with blood pressure control using ACE inhibitors or ARBs. Avoid nephrotoxins and provide supportive care. Hearing impairment may be aided with devices; ocular issues are managed per standard guidelines. In end-stage renal disease, dialysis or kidney transplantation is possible; graft recurrence is rare. Prognosis varies by genotype and sex; males with X-linked disease tend to have more severe progression.

History: The syndrome is named after Arthur C. Alport, who described it in 1927.