Rare Neurology News

Disease Profile

Alkaptonuria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adult

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ICD-10

E70.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

AKU; Alcaptonuria; Ochronosis, hereditary;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

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.

Symptoms

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]

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.

Medical Terms Other Names
Learn More:
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

Diagnosis

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.

Treatment

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]

Organizations

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).

      Learn more

      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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • MedlinePlus Genetics contains information on Alkaptonuria. This website is maintained by the National Library of Medicine.
      • 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.

          References

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

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