Alport syndrome is a hereditary renal disease, glomerulonephritis, resulting in renal failure. In addition, there is often (sensorineural) deafness and a congenital anomaly of the eye, a lenticonus. Alport syndrome is a genetic disease of collagen a3a4a5(IV). The collagen a3a4a5(IV) is a major component of the kidney glomerular basement membrane (GBM) as well as basement membranes in the cochlea (twisted tube inside the inner ear that is the main organ of hearing) and eye. Alport syndrome, estimated to affect 1 in 5000–10,000 individuals, is caused by changes (mutations changes) in any one of the three genes that encode the chain component of the collagen a3a4a5(IV): COL4A3, COL4A4, and COL4A5. The disease was first described by Dr. C Alport in 1924. Eighty percent of patients have an X-linked disease, caused by mutations in the COL4A5 gene. Most of these result in the replacement of the collagen IV α3α4α5 network with the α1α1α2 heterotrimer.
The term “Alport syndrome” is used for patients with the characteristic clinical features and a lamellated GBM with an abnormal collagen IV composition, and in whom a COL4A5 mutation (X-linked disease) or two COL4A3 or two COL4A4 mutations in trans (autosomal recessive disease) are identified or expected. Another clinical picture under the term “thin basement membrane nephropathy” (TBMN) is used for individuals with persistent isolated glomerular hematuria who have a thinned GBM due to a heterozygous COL4A3 or COL4A4 (but not COL4A5) mutation.