This rare, inherited deficiency of the enzyme homogentisic acid oxidase results in homogentisic acid reaching high levels in the body. This acid is excreted in the urine, which will then turn black if left to stand for a while because the acid oxidizes.

The diagnosis of alkaptonuria is suspected if a person gives a history of passing dark urine or of urine that becomes dark after standing for a while. Pigmented or dark-colored deposits of homogentisic acid collect in tissues such as cartilage that are rich in collagen, an important component of joints and soft tissues.

These pigmented deposits are called ochronosis. In early adult life, blue or black darkening of the ears or nose may occur. Homogentisic acid is also deposited in the cartilage of large joints such as the knees, resulting in osteoarthritis. It affects the cartilaginous discs between vertebrae, resulting in pain and stiffness of the spine.

On X ray these intervertebral discs are often heavily calcified. There is no specific treatment for the arthritis associated with alkaptonuria. High doses of vitamin C may slow the accumulation of pigment in tissues, but the effects of this treatment on the long-term arthritis problems are not known.