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Alkaptonuria (black urine disease, black bone disease, or alcaptonuria) is a rare inherited genetic disorder in which the body cannot process the amino acids phenylalanine and tyrosine, which occur in protein. It is caused by a mutation in the ''HGD'' gene for the enzyme homogentisate 1,2-dioxygenase (); if a person inherits abnormal copies from each parent (it is a recessive condition) the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidated form ''alkapton'' are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones and stones in other organs. Symptoms usually develop in people over thirty years old, although the dark discoloration of the urine is present from birth. Apart from treatment of the complications (such as pain relief and joint replacement for the cartilage damage), vitamin C has been used to reduce the ochronosis and lowering of the homogentisic acid levels may be attempted with a low-protein diet. Recently the drug nitisinone has been found to suppresses homogentisic acid production, and research is ongoing as to whether it can improve symptoms. Alkaptonuria is a rare disease; it occurs in one in 250,000 people, but is more common in Slovakia and the Dominican Republic. ==Signs and 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. Pigmentation may be noted in the cartilage of the ear as well as other cartilage,〔 and the sclera and corneal limbus of the eye. After the age of thirty people begin to develop pain in the weight-bearing joints of the spine, hips and knees. The pain can be severe to the point that interferes with activities of daily living and may affect 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. There is also a propensity to developing kidney stones, and eventually also gallstones and stones in the prostate and salivary glands (sialolithiasis).〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「alkaptonuria」の詳細全文を読む スポンサード リンク
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