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Alport syndrome

Alport syndrome
Classification & external resources
ICD-10 Q87.8
ICD-9 759.89
OMIM 301050 104200 203780 300195
DiseasesDB 454
MedlinePlus 000504
eMedicine med/110 
MeSH D009394

Alport syndrome is a genetic disorder characterized by glomerulonephritis, endstage kidney disease, and hearing loss. Alport syndrome can also affect the eyes. The presence of blood in the urine (hematuria) is almost always found in this condition.

It was first identified in a British family by Dr. Cecil A. Alport in 1927.



Alport syndrome is caused by mutations in COL4A3, COL4A4, and COL4A5, collagen biosynthesis genes. Mutations in any of these genes prevent the proper production or assembly of the type IV collagen network, which is an important structural component of basement membranes in the kidney, inner ear, and eye. Basement membranes are thin, sheet-like structures that separate and support cells in many tissues. When mutations prevent the formation of type IV collagen fibers, the basement membranes of the kidneys are not able to filter waste products from the blood and create urine normally, allowing blood and protein into the urine. The abnormalities of type IV collagen in kidney basement membranes cause gradual scarring of the kidneys, eventually leading to kidney failure in many people with the disease.

Inheritance patterns

Alport syndrome can have different inheritance patterns that are dependent on the genetic mutation.

  • In most people with Alport syndrome, the condition is inherited in an X-linked pattern, due to mutations in the COL4A5 gene. A condition is considered X-linked if the gene involved in the disorder is located on the X chromosome. In males, who have only one X chromosome, one altered copy of the COL4A5 gene is sufficient to cause severe Alport syndrome, explaining why most affected males eventually develop kidney failure. In females, who have two X chromosomes, a mutation in one copy of the COL4A5 gene usually results in blood in the urine, but most affected females do not develop kidney failure. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked diseases to their sons.
  • Alport syndrome can be inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, located on chromosome 2, have been mutated. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Criteria for the clinical diagnosis

Gregory et al, 1996, give the following 10 criteria for the diagnosis of Alport syndrome, 4 of the 10 criteria must be met:

  • Family history of nephritis of unexplained haematuria in a first degree relative of the index case or in a male relative linked through any numbers of females.
  • Persistent haematuria without evidence of another possibly inherited nephropathy such as thin GBM disease, polycystic kidney disease or IgA nephropathy.
  • Bilateral sensorineural hearing loss in the 2000 to 8000 Hz range. The hearing loss develops gradually, is not present in early infancy and commonly presents before the age of 30 years.
  • A mutation in COL4An (where n = 3, 4 or 5).
  • Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal basement membranes, or both.
  • Widespread GBM ultrastructural abnormalities, in particular thickening, thinning and splitting.
  • Ocular lesions including anterior lenticonus, posterior subcapsular cataract, posterior polymorphous dystrophy and retinal flecks.
  • Gradual progression to ESRD in the index case of at least two family members.
  • Macrothrombocytopenia or granulocytic inclusions.
  • Diffuse leiomyomatosis of esophagus or female genitalia, or both.


  • Kashtan CE. Michael AF. Alport syndrome. Kidney International. 50(5):1445-63, 1996 Nov.[1]
  • Tryggvason K. Heikkila P. Pettersson E. Tibell A. Thorner P. Can Alport syndrome be treated by gene therapy?. Kidney International. 51(5):1493-9, 1997 May.
  • Gregory MC et al: Alport syndrome clinical phenotypes, incidence and pathology, in Molecular Pathology and Genetics of Alport Syndrome (vol 117), edited by Tryggvason K, Basel, Karger, 1996, pp 1-28

This article incorporates public domain text from The U.S. National Library of Medicine

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Alport_syndrome". A list of authors is available in Wikipedia.
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