Alternative Names: Alcaptonuria; Homogentisic acid oxidase deficiency; Ochronosis

Causes, incidence, and risk factors:

Alkaptonuria is an autosomal recessive inherited disorder. In affected individuals, an amino acid known as tyrosine is not properly metabolized, due to a defect in an enzyme called homogentisic acid oxidase.

Because of the defect, homogentisic acid is excreted in the urine and turns a brown color upon exposure to air. This is the result of a dark pigment with an ochre color (earthy red or yellow), which led to the name ochronosis. The bones and cartilage of the body�may be brown-colored.

Symptoms:

Infant or child:

• Family history of alkaptonuria
• Urine in diaper may darken after several hours (can become almost black)

Adult:

• Progressive arthritis, especially of the spine
• Darkening of the ear (from black staining of the cartilage in the ear)
• Dark spots on the sclera (white of the eye) and cornea

Signs and tests:

Urinalysis is positive for reducing substance. Further urine testing shows a positive ferric chloride test.

Treatment:

Some patients benefit from high-dose vitamin C. This has been shown to decrease the build-up of brown pigment in the cartilage, which may slow the rate of development of arthritis.

Support Groups:

Expectations (prognosis):

The outcome is expected to be good.

Complications:

• Accumulation of homogentisic acid products in the cartilage causes arthritis in about 50% of older adults with alkaptonuria.
• Homogentisic acid products can accumulate on the heart valves, especially the mitral valve, sometimes leading to the need for valve replacement.
• Coronary artery disease may develop earlier in people with alkaptonuria.
• Kidney and prostate stones may be more common in people with alkaptonuria.

Calling your health care provider:

Call your health care provider if you notice that your own urine or your child's urine becomes dark brown or black upon exposure to air.

Prevention:

Like most genetic diseases, alkaptonuria itself cannot be prevented, but some of the manifestations, such as arthritis, can be minimized by treatment.