Ochronosis

Etiology

Ochronosis is the bluish-black discoloration that can be seen in connective tissues of patients with alkaptonuria, a rare disorder caused by the absence of homogentisic acid (HGA) oxidase. The absence of this enzyme causes a buildup of HGA in connective tissues, including the sclera, cornea, articular cartilage, intervertebral disks, tendons, and ligaments. The accumulated HGA is polymerized and oxidized, causing the characteristic pigmentation of the connective tissue. HGA or its oxidized form, benzoquinone, is also thought to physically bind to the connective tissue, thereby altering its structure.

Prevalence and Epidemiology

Ochronosis is a rare disorder, with a reported incidence between 1 in 250,000 and 1 in 1 million. The disease is hereditary, with an autosomal recessive pattern of inheritance. It affects both men and women, with a slight male predilection, and is typically asymptomatic until adulthood.

Clinical Presentation

Ochronosis may be discovered accidentally in infancy, with darkening of urine in diapers with exposure to air. Otherwise, patients present with pigmentation of sclerae and auricles around ages 20 to 30 years. The musculoskeletal manifestation of this process is termed ochronotic arthropathy , which is the most common clinical feature of alkaptonuria. Ochronotic arthropathy typically presents as pain and limitation of motion in the hip, knee, shoulder, or spine and usually occurs after age 40 years in patients with this disease and often progresses to complete disability in older patients.

Pathophysiology

There is blue-black pigmentation of connective tissue, including sclera, cornea, tracheal cartilage, bronchial cartilage, heart valves, articular cartilage, tendons, and ligaments.

Microscopically, there is intercellular and intracellular deposition of a pigment that chemically resembles melanin. Because of the pigment deposition and the altered structure, the connective tissues become progressively weak and brittle, leading to inflammation, degeneration, and fragmentation. Over time, the weakened intervertebral disks and hyaline cartilage are destroyed, resulting in the narrowing of the disk and joint spaces.