The pain can be severe to the point that interferes with activities of daily living and may affect the ability to work. Joint-replacement surgery (hip and shoulder) is often necessary at a relatively young age. In the longer term, the involvement of the spinal joints leads to reduced movement of the rib cage and can affect breathing. Bone mineral density may be affected, increasing the risk of bone fractures, and rupture of tendons and muscles may occur.Valvular heart disease, mainly calcification and regurgitation of the aortic and mitral valves, may occur, and in severe and progressive cases, valve replacement may be necessary. Irregularities in the heart rhythm and heart failure affect a significant proportion of people with alkaptonuria (40% and 10%, respectively). Hearing loss affects 40% of people. Also, a propensity to developing kidney stones exists, and eventually also gallstones and stones in the prostate and salivary glands (sialolithiasis) can occur. Pathophysiology
All people carry in their DNA two copies (one received from each parent) of the gene HGD, which contains the genetic information to produce the enzyme homogentisate 1,2-dioxygenase (HGD) which can normally be found in numerous tissues in the body (liver, kidney, small intestine, colon, and prostate). In people with alkaptonuria, both copies of the gene contain abnormalities that mean that the body cannot produce an adequately functioning enzyme. HGD mutations are generally found in certain parts (exons 6, 8, 10, and 13), but a total of over 100 abnormalities has been described throughout the gene.
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


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