Ochronosis (dark pigmentation in connective tissue) as the result of homogentisic acid (HGA) accumulation is a useful sign but does not appear until the 4th decade. As a result the joint cartilage becomes fragile leading to disabling and chronic symptoms of arthritis especially in the spine and large joints. Symptoms usually begin in the third or fourth decade and the degeneration of the ochronotic intervertebral disks may result in significant loss of height. Back pain, kyphosis, and decreased lumbar flexion are common. Usually smaller joints such as those of the digits are not affected sufficiently to cause symptoms.
Tendons, ligaments, and other fibrous tissue such as sclerae and heart valves are all susceptible to degenerative changes. The discoloration in skin hue can also be seen in the axillae, nail beds, pinnae, forehead, tympanic membranes, genital areas, and buccal mucosa. Clothing may become stained from discolored perspiration.
HGA in the urine oxidizes and turns dark and parents may note staining of diapers in the newborn period. The urine also becomes alkaline. Plasma levels of HGA are also elevated. Urolithiasis may occur.