Alkaptonuria is a rare metabolic disorder which was first described in 1902 by Sir Archibald Garrod. The three major features are arthritis, bluish-black pigmentation in connective tissue and urine that turns black when exposed to air. Individuals are affected differently by the range and severity of features. Alkaptonuria is found in all populations, however, it is especially frequent in individuals of Czech or Dominican descent. The condition affects males and females equally. Individuals are not usually aware of Alkaptonuria until their thirties and forties when symptoms become apparent. Children and young adults are usually asymptomatic.

Alkaptonuria is caused by the deficiency of an enzyme known as homogentisic acid oxidase (HGAO). Normally, this enzyme performs a crucial step in a metabolic pathway by converting a chemical, homogentisic acid (HGA), into another form to meet the body's needs. As normal amounts of the HGAO enzyme are missing, HGA is not broken-down and accumulates in the body. Some is eliminated in the urine, and the rest is deposited in body tissues where it is harmful. The result is a blue-black discolouration of connective tissue including bone, cartilage and skin (otherwise known as ochronosis).

The build-up of HGA leads to premature progressive degeneration in the joints. Chronic joint pain is one of the first symptoms of Alkaptonuria. Arthritis of the spine, knees and hips causes symptoms of stiffness, pain, swelling and limited motion. Males tend to have an earlier onset of arthritic symptoms with a greater degree of severity than females. Deposits of pigment may cause cartilage to become brittle and eventually to fragment.

Alkaptonuria may discolour the outer ears, nose and whites of the eyes with bluish-black pigment. Vision is not affected. The teeth and nails may also be a bluish-black colour. A dusky discolouration on the skin of the hands may be apparent. Pigment appears when individuals perspire, causing discolouration of clothing.

HGA accumulated in the urine causes this to turn black. Darkening may not occur for several hours after urinating and many individuals never observe any abnormal colour in their urine.

In later life, Alkaptonuria may affect the heart, kidney and prostate. The condition does not cause developmental delay or cognitive impairment and lifespan of affected individuals is generally not reduced.

Some of the symptoms of Alkaptonuria may be controlled with treatment.

Inheritance patterns
Alkaptonuria is inherited as an autosomal recessive trait. Changes in the HGD gene on chromosome 3 are associated with the features of Alkaptonuria. This condition was one of the first 'inborn errors of metabolism' and one of the first conditions for which recessive inheritance was proposed. Prenatal diagnosis
This may be possible and further information, including genetic counselling, should be sought from your doctor.

Medical text written September 2003 by Contact a Family. Approved September 2003 by Dr L Ranganath, Consultant Physician in Clinical Chemistry, Liverpool University Medical School, Liverpool, UK.

Further Online Resources
Medical texts in The Contact a Family Directory are designed to give a short, clear description of specific conditions and rare disorders. More extensive information on this condition can be found on a range of reliable, validated web sites and links to them are included in the CD-ROM version of this Directory. Further information on these resources can be found in our Medical Information on the Internet article.

Alkaptonuria Society
12 High Beeches
Childwall
Liverpool
L16 3GA
Tel: 0151 737 1862
e-mail: manager@alkaptonuria.info
Web: http://www.alkaptonuria.info

The Society provides support and information by phone and through the website. It has an online discussion board which is used by people from around the world.

Group details last confirmed May 2007.