AlkaptonuriaAKU; Alcaptonuria; Homogentisic acid oxidase deficiency; Alcaptonuric ochronosis
Alkaptonuria is a rare condition in which a person's urine turns a dark brownish-black color when exposed to air. Alkaptonuria is part of a group of conditions known as an inborn error of metabolism.
A defect in the HGD gene causes alkaptonuria.
The gene defect makes the body unable to properly break down certain amino acids (tyrosine and phenylalanine). As a result, a substance called homogentisic acid builds up in the skin and other body tissues. The acid leaves the body through the urine. The urine turns brownish-black when it mixes with air.
Alkaptonuria is inherited, which means it is passed down through families. If both parents carry a nonworking copy of the gene related to this condition, each of their children has a 25% (1 in 4) chance of developing the disease.
Urine in an infant's diaper may darken and can turn almost black after several hours. However, many people with this condition may not know they have it. The disease is most often discovered in mid-adulthood (around age 40), when joint and other problems occur.
Symptoms may include:
- Arthritis (especially of the spine) that gets worse over time
- Darkening of the ear
- Dark spots on the white of the eye and cornea
Exams and Tests
A urine test is done to test for alkaptonuria. If ferric chloride is added to the urine, it will turn the urine black in people with this condition.
Management of alkaptonuria has traditionally been focused on controlling symptoms. Eating a low protein diet may be helpful, but many people find this restriction difficult. Medicines, such as NSAIDs and physical therapy may help relieve joint pain.
Clinical trials are underway for other drugs to treat this condition and to assess whether the drug nitisinone provides long-term help with this illness.
The build-up of homogentisic acid in the cartilage causes arthritis in many adults with alkaptonuria.
- Homogentisic acid also can build up on the heart valves, especially the mitral valve. This can sometimes lead to the need for valve replacement.
- Coronary artery disease may develop earlier in life in people with alkaptonuria.
- Kidney stones and prostate stones may be more common in people with alkaptonuria.
Genetic counseling is recommended for people with a family history of alkaptonuria who are considering having children.
A blood test can be done to see if you carry the gene for alkaptonuria.
Prenatal tests (amniocentesis or chorionic villus sampling) can be done to screen a developing baby for this condition if the genetic change has been identified.
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Kliegman RM, St. Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM. Defects in metabolism of amino acids. In: Kliegman RM, St. Geme JW, Schor NF, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020:chap 103.
National Institutes of Health, National Library of Medicine. Long-term study of nitisinone to treat alkaptonuria. clinicaltrials.gov/ct2/show/NCT00107783. Updated January 19, 2011. Accessed May 4, 2019.
Riley RS, McPherson RA. Basic examination of urine. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St Louis, MO: Elsevier; 2017:chap 28.