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Alkaptonuria

Background

Alkaptonuria (AKU) is a rare metabolic disorder, which was first described in 1902 by Sir Archibald Garrod. The three major features of the condition 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. AKU is found in all populations, however, it is especially frequent in individuals of Slovaks or Dominican republic descent. The condition affects males and females equally. Individuals are not usually aware of AKU until their thirties and forties when symptoms become apparent. Children and young adults are usually asymptomatic (show no symptoms of the condition).

Credits

Medical text written September 2003 by Contact a Family. Approved September 2003 by Dr L Ranganath. Last updated September 2010 by Dr L Ranganath, Consultant Physician in Clinical Chemistry, Liverpool University Medical School, Liverpool, UK.

What are the symptoms?

AKU 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. Homogentisic acid (HGA) accumulated in the urine causes it 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, AKU 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.

What are the causes?

AKU 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 ochronosis (a blue-black discolouration of connective tissue, including bone, cartilage and skin.

The build-up of HGA leads to premature progressive degeneration in the joints. Chronic joint pain is one of the first symptoms of AKU. 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.

How is it diagnosed?

High degree of alertness is needed to recognise that black urine even early in life may be due to alkaptonouria. The presence of black urine in an older person with pigment in eye and ear should alert a clinician to consider the diagnosis. It can be confirmed by a simple urine test for high levels of HGA in a reliable laboratory.

How is it treated?

The main treatment at present is pain killers. When this fails, joint replacement will be required. There are at present no other approved treatments for AKU.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
AKUis inherited in an autosomal recessive manner. Changes in the HGD gene on chromosome 3 are associated with the features of AKU. This condition was one of the first 'inborn errors of metabolism' discovered 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 a doctor.

Is there support?

Alkaptonuria Society (AKU Society)

Tel: 01223 322 897
Email: info@akusociety.org
www.akusociety.org

The Society is a Registered Charity in England and Wales No. 1101052. It provides information and support to individuals and families affected by alkaptonuria (AKU).

Group details last updated August 2016.

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