This is caused by oxidation and polymerization of the homogentisic acid, and it is enhanced with an alkaline pH. Therefore, an acidic urine may not become dark even after many hours of standing. This is one of the reasons why darkening of the urine may perhaps never be noted in an affected person, and the diagnosis may be delayed until adulthood, when arthritis or ochronosis occurs. Homogentisic acid is a strong reducing agent that produces a positive reaction with Fehling or Benedict reagent, a feature that was also recognized in 1859. The diagnosis could also be confirmed by the high-pressure liquid chromatography method for the quantitation of homogentisic acid and its derivative benzoquinone acetic acid. 14 Measurement of this product by this method is used for therapy monitoring.
Alkaptonuric patients are usually asymptomatic as children or young adults.
When they get older, pigmentation of the sclera or the cartilage of the ear start to appear. Arthritis is the only disabling effect of this condition, and occurs in almost all patients with advancing age. The earliest symptoms are usually in the hips, spine and knees, the large weight-bearing joints. The arthritis has the clinical characteristics of rheumatoid arthritis, however, the radiological picture is of severe osteoarthritis. In contrast to osteoarthritis, the large joints at the hip and shoulder are most commonly involved, whereas the sacroiliac joint may be spared.