National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Alport syndrome


Other Names:
Alport syndrome, X-linked; Hemorrhagic familial nephritis; Hemorrhagic hereditary nephritis; Alport syndrome, X-linked; Hemorrhagic familial nephritis; Hemorrhagic hereditary nephritis; Congenital hereditary hematuria See More
Categories:
Subtypes:
Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. Most affected individuals experience progressive loss of kidney function, usually resulting in end-stage kidney disease. People with Alport syndrome also frequently develop sensorineural hearing loss in late childhood or early adolescence. The eye abnormalities characteristic of this condition seldom lead to vision loss. In 80% of cases, Alport syndrome is inherited in an X-linked manner and is caused by mutations in the COL4A5 gene. In the remaining cases, it may be inherited in either an autosomal recessive, or rarely in an autosomal dominant manner. In these cases, the condition is caused by mutations in the COL4A3 or COL4A4 genes.[1] Diagnosis of the condition is based on family history of the condition, clinical signs, and specific testing such as a kidney biopsy. The diagnosis can be confirmed by genetic testing. Treatment may include use of a hearing aid, hemodialysis and peritoneal dialysis to treat those with end-stage renal failure, and kidney transplantation.[1][2] 
Last updated: 3/18/2017
Alport syndrome is characterized by kidney disease, hearing loss, and eye abnormalities. Symptoms typically begin in childhood, and the first sign of the condition is usually the presence of blood in the urine (hematuria). Other symptoms of kidney disease can include having protein in the urine (proteinuria). Over time, an affected person may experience swelling (edema), bone weakening, and joint pain (osteodystrophy). Without treatment, affected individuals will experience end-stage renal disease.[1]

Alport syndrome also causes sensorineural hearing loss, or hearing loss that is due to the inner ear or the nerves not working properly. Hearing loss typically develops during late childhood or early adolescence, and most affected individuals become deaf by age 40. Alport syndrome is also characterized by specific eye changes. Most commonly, affected individuals have an eye finding called anterior lenticonus, which causes the lens to become cone-shaped. Other affected individuals may have abnormal coloration of the retina (dot-and-fleck retinopathy), which can sometimes lead to vision loss. Some individuals may experience maculopathy, or damage to the part of the eye (macula) that allows for central vision.[3][4] 
Last updated: 3/18/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 47 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Glomerulopathy 0100820
Hematuria
Blood in urine
0000790
Morphological abnormality of the semicircular canal 0011380
Retinopathy
Noninflammatory retina disease
0000488
Sensorineural hearing impairment 0000407
30%-79% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Dry skin 0000958
Dyspnea
Trouble breathing
0002094
Fatigue
Tired
Tiredness
[ more ] 		0012378
Headache
Headaches
0002315
Hypertension 0000822
Lentiglobus 0011527
Leukopenia
Decreased blood leukocyte number
Low white blood cell count
[ more ] 		0001882
Nephrotic syndrome 0000100
Pallor 0000980
Pedal edema
Fluid accumulation in lower limbs
Lower leg swelling
[ more ] 		0010741
Periorbital edema 0100539
Proteinuria
High urine protein levels
Protein in urine
[ more ] 		0000093
Renal insufficiency
Renal failure
Renal failure in adulthood
[ more ] 		0000083
Tinnitus
Ringing in ears
Ringing in the ears
[ more ] 		0000360
Weight loss 0001824
5%-29% of people have these symptoms
Abdominal situs inversus 0003363
Corneal dystrophy 0001131
Diffuse leiomyomatosis 0006756
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty
[ more ] 		0002015
Macular dystrophy 0007754
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Neoplasm of the colon
Colon tumor
0100273
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity
[ more ] 		0000613
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin
[ more ] 		0001482
Thrombocytopenia
Low platelet count
0001873
Uterine neoplasm
Uterine tumor
0010784
Vomiting
Throwing up
0002013
Percent of people who have these symptoms is not available through HPO
Anterior lenticonus 0011501
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Developmental cataract
Clouding of the lens of the eye at birth
0000519
Diffuse glomerular basement membrane lamellation 0030034
Hypoparathyroidism
Decreased parathyroid hormone secretion
0000829
Ichthyosis 0008064
Lenticonus 0001142
Microscopic hematuria
Small amount of blood in urine
0002907
Nephritis
Kidney inflammation
0000123
Progressive
Worsens with time
0003676
Stage 5 chronic kidney disease 0003774
Thickening of the glomerular basement membrane 0004722
X-linked dominant inheritance 0001423
X-linked inheritance 0001417
Showing of 47 |
Last updated: 7/1/2020
Alport syndrome is caused by mutations in three possible genes: COL4A3, COL4A4, or COL4A5. These genes each provide instructions for making one component of a protein called type IV collagen, which plays an important role in the glomeruli of the kidneys. Glomeruli are clusters of specialized blood vessels that remove water and waste products from the blood and create urine. Mutations in the genes associated with Alport syndrome result in abnormalities of the type IV collagen in glomeruli, which prevent the kidneys from properly filtering the blood. As a result, blood and protein pass into the urine. Over time, the kidneys become scarred, which leads to kidney failure.[1][2]

Type IV collagen is also an important component of the organ of Corti, the inner ear structure that transforms sound waves into nerve impulses for the brain. Alterations in type IV collagen may result in abnormal inner ear functions, which can lead to hearing loss. In addition, type IV collagen plays a role in the eye, where it helps maintain the shape of the lens and the cells of the retina. Mutations found in Alport syndrome may affect the retina and the shape of the lens.[1] 
Last updated: 3/18/2017
Alport syndrome can be inherited in three different ways. About 80 percent of cases are caused by mutations in the COL4A5 gene and are inherited in an X-linked recessive pattern. The COL4A5 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 only one copy of the COL4A5 gene usually only results in hematuria. However, some women experience more severe symptoms such as kidney failure or hearing loss. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[1]

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. Males and females are equally affected by the autosomal recessive form of Alport syndrome.[1]

Alport syndrome is rarely inherited as an autosomal dominant condition. People with this form of Alport syndrome have one mutation in either COL4A3 or COL4A4 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 or no symptoms at all.[1][4]
Last updated: 3/18/2017
Alport syndrome is suspected based on a family history or clinical signs of the condition. A doctor may order a kidney biopsy to look for signs of the condition such as abnormalities of the cells of the glomeruli. A kidney biopsy can also allow to test specifically for type IV collagen protein, as this protein would be absent in a person with Alport syndrome. Doctors may also order a test to measure the amount of blood and protein in the urine. An ophthalmologic exam may be used to look for signs characteristic of the condition such as anterior lenticonus. When Alport syndrome is suspected, genetic testing can be used to confirm the diagnosis and determine the pattern of inheritance. This can provide information about the chance that other family members are affected.[2][5] 
Last updated: 3/18/2017
Although there is no one specific treatment for Alport syndrome, the goals of treatment include monitoring and controlling progression of the disease and treating the symptoms. Strict control of blood pressure is very important in order to keep the kidneys as healthy as possible. Research suggests that ACE inhibitors, angiotensins, and statins can help reduce proteinuria and the progression of kidney disease. However, treatment of chronic kidney failure often becomes necessary. This can include dietary modifications and fluid restriction. Ultimately, chronic kidney failure progresses to end-stage kidney disease, requiring dialysis or transplantation. Kidney transplantation in people with Alport syndrome is usually successful, but some studies have reported that about 10% of transplanted patients develop inflammation of the kidneys (nephritis).[3][4]

Treatment for other aspects of the condition are addressed as needed. For instance, surgical repairs of the eye manifestations may be recommended. Loss of hearing is likely to be permanent, but affected individuals can be assisted with hearing aids. Counseling and education to increase coping skills can be helpful. Learning new skills such as lip reading or sign language may be of some benefit. Young men with Alport syndrome should use hearing protection in noisy environments. Genetic counseling may be recommended to explain the inherited pattern of the disorder.[2] 

 

Additional information related to the treatment of Alport syndrome can be accessed through GeneReviews and eMedicine. 

Last updated: 3/18/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Alport syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Alport syndrome. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Alport syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I was just diagnosed with Alport syndrome as an adult. Is this more common in those of Ashkenazi Jewish ancestry? See answer

  • What damage does Alport syndrome do to the kidney? See answer

  • My son rejected his first kidney transplant, can I be a donor since I am also a carrier? See answer

  • My sister's daughter has a son with X-linked Alport syndrome. Although my niece was not genetically tested as a carrier, her doctor assumed she is a carrier because of the large amount of blood in her urine. I have 2 sons and one daughter. I am told that my sons cannot be carriers and therefore don't have to worry about passing on this syndrome. Is that true? Also, how about my daughter? I have not been tested but if I do get tested and am not a carrier, then can I assume she is ok and will not pass down the syndrome to her children? Also, if I have my urine tested for hematuria and I don't have blood, can I assume that I am not a carrier? See answer

  • What causes Alport syndrome? Is it always inherited? See answer

  • I have been on hemodialysis for a year as a result of Alport syndrome. My two uncles died of kidney disease associated with this condition. What treatments are available for this condition? See answer


  1. Alport syndrome. Genetics Home Reference. December 2013; http://ghr.nlm.nih.gov/condition/alport-syndrome.
  2. Meroni M and Sessa A. Alport syndrome. Orphanet. July 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=63.
  3. Silberberg C. Alport syndrome. MedlinePlus. September 22, 2015; http://www.nlm.nih.gov/medlineplus/ency/article/000504.htm.
  4. Saxena R. Alport Syndrome. Medscape Reference. July 21, 2015; http://emedicine.medscape.com/article/238260-treatment#showall.
  5. Kashtan CE. Alport Syndrome and Thin Basement Membrane Nephropathy. GeneReviews. November 25, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1207/.