Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase (EC 1.13.11.5); if a person inherits an abnormal copy from both parents (it is a recessive condition), the body accumulates an intermediate substance called homogentisic acid in the blood and tissues.

Apart from treatment of the complications (such as pain relief and joint replacement for the cartilage damage), the drug nitisinone has been found to suppress homogentisic acid production, and research is ongoing as to whether it can improve symptoms.

Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air.

[1] In the longer term, the involvement of the spinal joints leads to reduced movement of the rib cage and can affect breathing.

In people with alkaptonuria, both copies of the gene contain abnormalities that mean that the body cannot produce an adequately functioning enzyme.

[1] If the diagnosis of alkaptonuria is suspected, it can be confirmed or excluded by collecting urine for 24 hours and determining the amount of homogentisic acid by means of chromatography.

[citation needed] Nitisinone has revolutionised the treatment of AKU, however it can lead to a condition known as hypertyrosinaemia[6] caused by elevated levels of the amino acid tyrosine.

Hypertyrosinaemia can lead to serious symptoms including corneal keratopathy,[7] dermal toxicity,[8] neurodevelopment delay issues in children,[9] and alterations of wider metabolism.

Due to the potential side-effects of nitisinone treatment it is currently only prescribed to children aged 16 and above in Europe and patients will then have to follow a protein restricted diet and closely manage their tyrosine levels through frequent monitoring.

[4] Alkaptonuria was one of the four diseases described by Archibald Edward Garrod, as being the result of the accumulation of intermediates due to metabolic deficiencies.

He linked ochronosis with the accumulation of alkaptans in 1902,[4][11] and his views on the subject, including its mode of heritance, were summarized in a 1908 Croonian Lecture at the Royal College of Physicians.

[citation needed] The AKU Society works to provide information, education, support, and helps people to access treatment for their condition.

[citation needed] Research collaborations by several national centres have been established to find a more definitive treatment for alkaptonuria.