Hereditary nephritis (or Alport syndrome) is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities [1-4]. The prevalence of the disease is estimated at approximately 1 in 50,000 live births . Alport syndrome reportedly accounts for 0.3 to 2.3 percent of new cases of end-stage renal disease (ESRD) [6,7].
The pathogenesis, genetics, and renal pathology of Alport syndrome will be reviewed here. The clinical manifestations and course, diagnosis, and treatment of Alport syndrome are discussed separately. (See "Clinical manifestations, diagnosis and treatment of hereditary nephritis (Alport syndrome)".)
Elucidation of the pathogenesis of Alport syndrome was facilitated by the chance observation that the glomerular basement membrane (GBM) of most affected patients did not bind antibodies from patients with anti-GBM antibody disease (including Goodpasture's syndrome) [3,8-10]. This finding suggested an abnormality in type IV collagen, the protein target of anti-GBM antibodies. Subsequent research efforts confirmed that the primary abnormality resides in type IV collagen as discussed in the following section.
Genetics — Alport syndrome is a primary basement membrane disorder arising from mutations in genes encoding several members of the type IV collagen protein family.
Type IV collagen molecules are composed of three alpha chains that form triple-helical structures through specific interactions of C-terminal noncollagenous domains . Six distinct IV collagen chains are encoded by six different genes that are distributed in head-to-head pairs on three chromosomes.