Alkaptonuria (black urine disease or alcaptonuria) is a rare inherited genetic disorder of phenylalanine and tyrosine metabolism. This is an autosomal recessive condition that is due to a defect in the enzyme homogentisate 1,2-dioxygenase (EC 188.8.131.52), which participates in the degradation of tyrosine. As a result, homogentisic acid and its oxide, called alkapton, accumulate in the blood and are excreted in urine in large amounts (hence -uria). Excessive homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones. Treatment with nitisinone, which suppresses homogentisic acid production, is being studied. Alkaptonuria is more common in Slovakia and the Dominican Republic than in other countries.
Alkaptonuria is often asymptomatic, but the sclera of the eyes may be pigmented (often only at a later age), and the skin may be darkened in sun-exposed areas and around sweat glands; sweat may be coloured brown. Urine may turn brown or even inky black if collected and left exposed to open air, especially when left standing for a period of time. Kidney stones and stone formation in the prostate (in men) are common and may occur in more than a quarter of cases.
The main symptoms of alkaptonuria are due to the accumulation of homogentisic acid in tissues. In the joints this leads to cartilage damage, specifically in the spine, leading to low back pain at a young age in most cases. Cartilage damage may also occur in the hip and shoulder. Joint replacement surgery (hip and shoulder) is often necessary at a relatively young age.
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. Coronary artery disease may be accelerated in alkaptonuria.
A distinctive characteristic of alkaptonuria is that ear wax exposed to air turns red or black (depending on diet) after several hours because of the accumulation of homogentisic acid.