Alport syndrome is a type IV collagen disease that affects the glomerular basement membrane of approximately one in every 5000 people. The disease was first described by A. Cecil Alport in 1927 as “a dominantly inherited hereditary nephritis.” The three genotypes of the disease are X-linked dominant, autosomal recessive, and autosomal dominant. The X-linked dominant genotype is the most common, accounting for 80% of all cases of Alport syndrome, affecting mainly men. The autosomal recessive and autosomal dominant types affect men and women equally. Alport syndrome is caused by mutations on the COL4A3, COL4A4, and COL4A5 genes, which code the ?3, ?4, and ?5 (IV) chains that make up type IV collagen molecules, an important component of basement membranes. Thus, Alport syndrome results in malformed basement membranes, with symptoms including renal impairment, hematuria, bilateral sensorineural hearing loss, and an abnormal structure of the glomerular basement membrane. Alport syndrome also often progresses to end-stage renal disease, especially in men with X-linked Alport syndrome. At this point, there is no cure for Alport syndrome. However, there are many successful treatments for its symptoms. Angiotensin-converting enzyme (ACE) inhibitors are often given to patients in the early stages of Alport syndrome. For patients with end-stage renal disease, dialysis or kidney transplants are considered the best course of action.
Structure of the Human Type IV Collagen Gene COL4A3 and Mutations in Autosomal Alport Syndrome