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Alport syndrome
Classification and 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[1] characterized by glomerulonephritis, endstage kidney disease, and hearing loss.[2] 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,[3][4] though William Howship Dickinson is also considered by some to have made contributions to the characterization.[5]



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. Progression of the disease leads to basement membrane thickening and gives a "basket-weave" appearance from splitting of the lamina densa. Single molecule computational studies of type IV collagen molecules have shown changes in the structure and nanomechanical behavior of mutated molecules, notably leading to a bent molecular shape with kinks [6].

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.
  • Past descriptions of an autosomal dominant form are now usually categorized as other conditions, [7] though some uses of the term in reference to the COL4A3 and COL4A4 loci have been published.[8][9]

Criteria for the clinical diagnosis

Gregory et al., 1996, gave the following 10 criteria for the diagnosis of Alport syndrome,[10] 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.

The use of eye examinations for screening has been proposed.[11]


Gene therapy as a possible treatment option has been discussed.[12]


  1. ^ Diseases of the Kidney: Alport Syndrome
  2. ^ Alport syndrome at Dorland's Medical Dictionary
  3. ^ Lagona E, Tsartsali L, Kostaridou S, Skiathitou A, Georgaki E, Sotsiou F (April 2008). "Skin Biopsy for the diagnosis of Alport Syndrome". Hippokratia 12 (2): 116–8. PMID 18923659.  
  4. ^ A. C. Alport. Hereditary familial congenital haemorrhagic nephritis. British Medical Journal, London, 1927, I: 504-506.
  5. ^ synd/337 at Who Named It?
  6. ^ Srinivasana M, Uzel SGM, Gautieri A, Keten S, Buehler MJ (2009). "Alport Syndrome mutations in type IV tropocollagen alter molecular structure and nanomechanical properties". J. Structural Biology 168 (3): 503-510. doi:10.1016/j.jsb.2009.08.015.  
  7. ^ "OMIM - ALPORT SYNDROME, AUTOSOMAL DOMINANT". Retrieved 2008-11-24.  
  8. ^ Kharrat M, Makni S, Makni K, et al. (September 2006). "Autosomal dominant Alport's syndrome: study of a large Tunisian family". Saudi J Kidney Dis Transpl 17 (3): 320–5. PMID 16970251.;year=2006;volume=17;issue=3;spage=320;epage=325;aulast=Kharrat.  
  9. ^ Pescucci C, Mari F, Longo I, et al. (May 2004). "Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene". Kidney Int. 65 (5): 1598–603. doi:10.1111/j.1523-1755.2004.00560.x. PMID 15086897.  
  10. ^ Gregory MC, Terreros DA, Barker DF, Fain PN, Denison JC, Atkin CL (1996). "Alport syndrome--clinical phenotypes, incidence, and pathology". Contrib Nephrol 117: 1–28. PMID 8801040.  
  11. ^ Zhang KW, Colville D, Tan R, et al. (August 2008). "The use of ocular abnormalities to diagnose X-linked Alport syndrome in children". Pediatr. Nephrol. 23 (8): 1245–50. doi:10.1007/s00467-008-0759-4. PMID 18343956.  
  12. ^ Tryggvason K, Heikkilä P, Pettersson E, Tibell A, Thorner P (1997). "Can Alport syndrome be treated by gene therapy?". Kidney Int. 51 (5): 1493–9. doi:10.1038/ki.1997.205. PMID 9150464.  

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

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