Nitisinone has been used for some time at much higher doses in the treatment of type I tyrosinemia. Nitisinone treatment has been shown to cause a larger than 95% reduction in plasma and urinary HGA. The main drawback is accumulation of tyrosine, the long-term risks of which are unknown; a particular concern exists about damage to the cornea of the eye. Long-term use requires frequent monitoring for complications. Prognosis
Alkaptonuria does not appear to affect life expectancy, although the latest study on the topic is from 1985. The main impact is on quality of life; many people with alkaptonuria have disabling symptoms such as pain, poor sleep, and breathing symptoms. These generally start in the fourth decade. The typical age at requiring joint replacement surgery is 50–55 years. Epidemiology
In most ethnic groups, the prevalence of alkaptonuria is between 1:100,000 and 1:250,000. In Slovakia and the Dominican Republic, the disease is much more common, with prevalence estimated at 1:19,000 people. As for Slovakia, this is not the result of a single mutation, but due to a group of 12 mutations in specific "hot spots" of the HGD gene. The Slovakian clustering probably arose in a small area in the northwest of the country and spread after the 1950s due to migration. History
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, and his views on the subject, including its mode of heritance, were summarized in a 1908 Croonian Lecture at the Royal College of Physicians. The genetics of it was also studied by William Bateson in the 1902.The defect was narrowed down to homogentisic acid oxidase deficiency in a study published in 1958. The genetic basis was elucidated in 1996, when HGD mutations were demonstrated.A 1977 study showed that an ochronotic Egyptian mummy had probably suffered from alkaptonuria. Research directions
Research collaborations by several national centres have been established to find a more definitive treatment for alkaptonuria. This has included studies on the use of nitisinone and investigations into antioxidants to inhibit ochronosis. The ideal treatment would replace HGD enzyme function without accumulating other substances. See also
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions

References


== External links ==