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Alport syndrome

Reviewed April 2009

What is Alport syndrome?

Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.

People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD).

People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue at the back of the eye (retina). These eye abnormalities seldom lead to vision loss.

Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females.

How common is Alport syndrome?

Alport syndrome occurs in approximately 1 in 50,000 newborns.

What genes are related to Alport syndrome?

Mutations in the COL4A3, COL4A4, and COL4A5 genes cause Alport syndrome. These genes each provide instructions for making one component of a protein called type IV collagen. This protein plays an important role in the kidneys, specifically in structures called glomeruli. Glomeruli are clusters of specialized blood vessels that remove water and waste products from blood and create urine. Mutations in these genes result in abnormalities of the type IV collagen in glomeruli, which prevents the kidneys from properly filtering the blood and allows blood and protein to pass into the urine. Gradual scarring of the kidneys occurs, eventually leading to kidney failure in many people with Alport syndrome.

Type IV collagen is also an important component of inner ear structures, particularly the organ of Corti, that transform sound waves into nerve impulses for the brain. Alterations in type IV collagen often result in abnormal inner ear function, which can lead to hearing loss. In the eye, this protein is important for maintaining the shape of the lens and the normal color of the retina. Mutations that disrupt type IV collagen can result in misshapen lenses and an abnormally colored retina.

How do people inherit Alport syndrome?

Alport syndrome can have different inheritance patterns. About 80 percent of cases are caused by mutations in the COL4A5 gene and are inherited in an X-linked pattern. This gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the COL4A5 gene in each cell is sufficient to cause kidney failure and other severe symptoms of the disorder. In females (who have two X chromosomes), a mutation in one copy of the COL4A5 gene usually only results in hematuria, but some women experience more severe symptoms. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In approximately 15 percent of cases, Alport syndrome results from mutations in both copies of the COL4A3 or COL4A4 gene and is inherited in an autosomal recessive pattern. The parents of an individual with the autosomal recessive form of this condition each have one copy of the mutated gene and are called carriers. Some carriers are unaffected and others develop a less severe condition called thin basement membrane nephropathy, which is characterized by hematuria.

Alport syndrome has autosomal dominant inheritance in about 5 percent of cases. People with this form of Alport syndrome have one mutation in either the COL4A3 or COL4A4 gene in each cell. It remains unclear why some individuals with one mutation in the COL4A3 or COL4A4 gene have autosomal dominant Alport syndrome and others have thin basement membrane nephropathy.

Where can I find information about treatment for Alport syndrome?

You may find information on treatment or management of Alport syndrome or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about Alport syndrome?

You may find the following resources about Alport syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Alport syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/000504.htm)
    • Encyclopedia: End-stage kidney disease (http://www.nlm.nih.gov/medlineplus/ency/article/000500.htm)
    • Health Topic: Kidney Diseases (http://www.nlm.nih.gov/medlineplus/kidneydiseases.html)
    • Health Topic: Kidney Failure (http://www.nlm.nih.gov/medlineplus/kidneyfailure.html)
  • Additional NIH Resources - National Institutes of Health
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.263)
    • National Institute of Diabetes and Digestive and Kidney Diseases (http://kidney.niddk.nih.gov/kudiseases/pubs/glomerular/index.htm#alport)
  • Educational resources - Information pages
    • Alport Syndrome Treatments and Outcomes Registry (ASTOR) (http://www.med.umn.edu/peds/nephr/astor/)
    • Ask the Geneticist (http://genetics.emory.edu/ask/question.php?question_id=5569)
    • Boys Town National Research Hospital (http://www.boystownhospital.org/Hearing/info/genetics/syndromes/alport.asp)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,374/)
    • Merck Manual Home Edition for Patients and Caregivers (http://www.merck.com/mmhe/sec11/ch144/ch144b.html#CIHEEIJG)
    • National Kidney Foundation (http://www.kidney.org/atoz/atozItem.cfm?id=47)
    • New York Online Access to Health (NOAH) (http://www.noah-health.org/en/kidver/kidney/specific/alport.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=63)
  • Patient support - For patients and families
    • Alport Syndrome Foundation (https://www.alportsyndrome.org)
    • American Association of Kidney Patients (http://www.aakp.org/aakp-library/Alport-Syndrome/)
    • Genetic Alliance (http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Alport%20Syndrome&expand=Treatment)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Alport%20Syndrome)
    • The Kidney Foundation of Canada (http://www.kidney.ca/page.asp?intNodeId=22140)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=alport)
  • Gene Tests - DNA tests ordered by healthcare professionals
    • Gene Tests: Alport Syndrome, X-Linked (http://www.genetests.org/query?testid=2306)
    • Gene Tests: COL4A3 Alport Syndrome and Thin Basement Membrane Nephropathy (http://www.genetests.org/query?testid=2873)
    • Gene Tests: COL4A4 Alport Syndrome and Thin Basement Membrane Nephropathy (http://www.genetests.org/query?testid=68834)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22alport+syndrome%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Nephritis,+Hereditary[MAJR])+AND+(Alport+syndrome[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1080+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Alport Syndrome and Basement Membrane Collagen (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=214)
  • OMIM - Genetic disorder catalog
    • OMIM topic: Alport syndrome, autosomal dominant (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104200)
    • OMIM topic: Alport syndrome, autosomal recessive (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=203780)
    • OMIM topic: Alport syndrome, X-Linked (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=301050)

What other names do people use for Alport syndrome?

  • congenital hereditary hematuria
  • hematuria-nephropathy-deafness syndrome
  • hematuric hereditary nephritis
  • hemorrhagic familial nephritis
  • hemorrhagic hereditary nephritis
  • hereditary familial congenital hemorrhagic nephritis
  • hereditary hematuria syndrome
  • hereditary interstitial pyelonephritis
  • Hereditary nephritis

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Alport syndrome?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding Alport syndrome?

anterior ; autosomal ; autosomal dominant ; autosomal recessive ; carrier ; cell ; chromosome ; chronic ; collagen ; congenital ; end-stage renal disease ; ESRD ; familial ; gene ; glomerulus ; hematuria ; inheritance ; inheritance pattern ; kidney ; mutation ; nephritis ; nephropathy ; protein ; proteinuria ; recessive ; renal ; renal disease ; retina ; sensorineural ; sensorineural hearing loss ; sex chromosomes ; stage ; symptom ; syndrome ; tissue ; trait

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Ierino FL, Kanellis J. Thin basement membrane nephropathy and renal transplantation. Semin Nephrol. 2005 May;25(3):184-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15880331)
  • Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study. J Am Soc Nephrol. 2003 Oct;14(10):2603-10. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14514738)
  • Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Verellen C, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC. X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol. 2000 Apr;11(4):649-57. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10752524)
  • Kashtan CE. Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy. Curr Opin Pediatr. 2004 Apr;16(2):177-81. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15021198)
  • Kashtan CE. Familial hematurias: what we know and what we don't. Pediatr Nephrol. 2005 Aug;20(8):1027-35. Epub 2005 Apr 27. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15856317)
  • Kashtan CE. The nongenetic diagnosis of thin basement membrane nephropathy. Semin Nephrol. 2005 May;25(3):159-62. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15880326)
  • Merchant SN, Burgess BJ, Adams JC, Kashtan CE, Gregory MC, Santi PA, Colvin R, Collins B, Nadol JB Jr. Temporal bone histopathology in alport syndrome. Laryngoscope. 2004 Sep;114(9):1609-18. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15475791)
  • Pescucci C, Longo I, Bruttini M, Mari F, Renieri A. Type-IV collagen related diseases. J Nephrol. 2003 Mar-Apr;16(2):314-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12768082)
  • Slajpah M, Gorinsek B, Berginc G, Vizjak A, Ferluga D, Hvala A, Meglic A, Jaksa I, Furlan P, Gregoric A, Kaplan-Pavlovcic S, Ravnik-Glavac M, Glavac D. Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int. 2007 Jun;71(12):1287-95. Epub 2007 Mar 28. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17396119)
  • Thorner PS. Alport syndrome and thin basement membrane nephropathy. Nephron Clin Pract. 2007;106(2):c82-8. Epub 2007 Jun 6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17570934)
  • Wang YY, Rana K, Tonna S, Lin T, Sin L, Savige J. COL4A3 mutations and their clinical consequences in thin basement membrane nephropathy (TBMN). Kidney Int. 2004 Mar;65(3):786-90. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14871398)
  • Zehnder AF, Adams JC, Santi PA, Kristiansen AG, Wacharasindhu C, Mann S, Kalluri R, Gregory MC, Kashtan CE, Merchant SN. Distribution of type IV collagen in the cochlea in Alport syndrome. Arch Otolaryngol Head Neck Surg. 2005 Nov;131(11):1007-13. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16301374)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2009
Published: May 4, 2009