In alkaptonuria, the accumulation of HGA inhibits collagen cross-linking by affecting a crucial enzyme in collagen synthesis, leading to a diminution of structural collagen integrity. The larger joints are most affected with early calcification, narrowing and collapse of the intervertebral discs. In addition to joint disease, there are reports suggesting increased incidence of cardiovascular disease due to cartilaginous changes of vessel walls. Homogentisic acid oxidase requires atmospheric oxygen, ferrous ion and sulfhydryl groups for normal function, and the enzyme is inhibited by quinones. Individuals with acidic urine may not demonstrate the very dark colored urine characteristic of this condition.
Alkaptonuria is seen in all races.
There is an equal incidence of alkaptonuria in both sexes. Alkaptonuria is often recognized at birth when parents note discoloration of the urine. These ocular discolorations are located between the corneal margin and the inner canthus. Ochronotic arthropathy later develops with arthritic symptoms. For those cases of alkaptonuria not diagnosed in infancy, black cerumen and axillary pigmentation may be noted before the age of 10.