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

Alkaptonuria


Other Names:
AKU; Alcaptonuria; Ochronosis, hereditary; AKU; Alcaptonuria; Ochronosis, hereditary; Alkaptonuric ochronosis; Homogentisic acid oxidase deficiency; Homogentisic acidura See More
Categories:
Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. The three major features of alkaptonuria are the presence of dark urine, ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, and arthritis of the spine and larger joints. Ochronosis starts after age 30 and arthritis in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones. Alkaptonuria is caused by mutations in the HGD gene. It is inherited in an autosomal recessive fashion.[1] There is still no cure for this disease. Treatment includes the management of joint pain, physical and occupational therapy, joint replacements and surgery when needed.
Last updated: 3/18/2016
The three main features of alkaptonuria (AKU) are the presence of  a substance called homogentisic acid (HGA) in the urine, ochronosis and arthritis. The urine of individuals with AKU turns black when exposed to air. Children do not have symptoms of AKU other than the urine turning black when left to stand for a few minutes. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30 and commonly affects the cartilage of the ear, ligaments, tendons, blood vessels, kidneys, lungs and prostate. Dark spots on the white of the eye and cornea may also occur. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, changes of the sound of the voice and prostate stones.[1][2][3]
Last updated: 3/18/2016

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 39 |
Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Abnormality of vision
Abnormality of sight
Vision issue
[ more ] 		0000504
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine
[ more ] 		0003355
Arthralgia
Joint pain
0002829
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Calcification of cartilage 0100593
Coronary artery calcification 0001717
Hearing abnormality
Abnormal hearing
0000364
Intervertebral disk calcification 0005645
Irregular hyperpigmentation 0007400
Joint dislocation
Joint dislocations
Recurrent joint dislocations
[ more ] 		0001373
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Joint swelling 0001386
Osteoarthritis
Degenerative joint disease
0002758
30%-79% of people have these symptoms
Abnormality of the nail 0001597
Abnormality of the nose
Nasal abnormality
0000366
Aortic valve calcification 0004380
Cartilage destruction 0100773
Mitral valve calcification 0004382
Nephrolithiasis
Kidney stones
0000787
Prostatitis
Inflammation of the prostate
0000024
Tendon rupture
Rupture of tendons
Ruptured tendon
[ more ] 		0100550
Thickened Achilles tendon 0004690
5%-29% of people have these symptoms
Atherosclerosis
Narrowing and hardening of arteries
0002621
Hypertension 0000822
Myocardial infarction
Heart attack
0001658
Reduced bone mineral density
Low solidness and mass of the bones
0004349
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Abnormality of the ear 0000598
Abnormality of the urinary system
Urinary tract abnormalities
Urinary tract abnormality
Urinary tract anomalies
[ more ] 		0000079
Aortic aneurysm
Bulge in wall of large artery that carries blood away from heart
0004942
Arthritis
Joint inflammation
0001369
Arthropathy
Disease of the joints
0003040
Autosomal recessive inheritance 0000007
Back pain 0003418
Growth abnormality
Abnormal growth
Growth issue
[ more ] 		0001507
Intervertebral disc degeneration 0008419
Kyphosis
Hunched back
Round back
[ more ] 		0002808
Pigmentation of the sclera 0007832
Vertebral fusion
Spinal fusion
0002948
Showing of 39 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

There is no cure for alkaptonuria, but there is treatment for some individual signs and symptoms of the condition. Joint pain may be substantial in individuals with alkaptonuria, and close attention to pain control is usually necessary. Physical and occupational therapy can be important to promote muscle strength and flexibility. Knee, hip, and shoulder replacement surgeries may be options for managing significant arthritis. In general, however, the goal of joint replacement is pain relief rather than increased range of motion. Maintaining joint range of motion through moderate non-weight-bearing exercise such as swimming may have beneficial effects. Treatment of prostate stones and renal stones may include surgery.[4]

No therapy has proven to prevent or correct the pigmentary changes of ochronosis.[4] 

Dietary restriction of phenylalanine and tyrosine has been proposed to reduce the production of HGA, but severe restriction of these amino acids is not practical in the long term and may be dangerous.[4]
Last updated: 3/18/2016

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

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes acute intermittent porphyria, rheumatoid arthritis, ankylosing spondylitis and osteoarthritis.
Visit the Orphanet disease page for more information.

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 Alkaptonuria. 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

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

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 Alkaptonuria. 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 Alkaptonuria. 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.

  1. Alkaptonuria. Genetics Home Reference (GHR). 2013; http://ghr.nlm.nih.gov/condition=alkaptonuria.
  2. Alkaptonuria. MedlinePlus. March 2, 2016; http://www.nlm.nih.gov/medlineplus/ency/article/001200.htm.
  3. Timmis O. Alkaptonuria. AKU Society. 2016; http://www.rarediseasesindia.org/aku.
  4. Introne WJ, Kayser MA & Gahl WA. Alkaptonuria. GeneReviews. August 22, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1454/.