...less medical jargon in a 'Quick Glance' format!
Ochronosisis a metabolic disorder in which homogentisic acid oxidase is absent. Therefore, homogentisic acid accumulates in cartilage and connective tissues. This deposition of dark pigment is known as ochronosis.
Symptoms: The outward signs are the eye and the skin pigmentations, the genito-urinary calculi (stones) and especially the aortic valve). The symptoms mostly begin within the third or fourth decade.
Causes: This is an autosomal recessive inherited disorder, which means that two abnormal genes (one from each parent) are needed to have the disease. The defect causes the body not to produce enough of an enzyme called homogentisic acid oxidase. This enzyme normally breaks down a toxic by-product of tyrosine metabolism called homogentisic acid. Although some of this is excreted in urine, small amounts remain in the body and slowly and progressively get deposited in bones and cartilage where it turns into a pigmented polymeric material.
It may also be caused by external agents. These may include:
Medications such as quinacrine and quinine
Deposits of carboxylic acid, used in the past to treat leg ulcers
Rarely, excessive use of hydroquinone (in this case, cartilage is not affected).
Treatment:
This disease is a lifelong disease. There is no cure for the condition. If alkaptonuria is diagnosed early on in life it is reasonable for patients to have a low-protein diet. This reduces the intake of amino acids phenylalanine and tyrosine, which in turn reduces the amount of homogentisic acid produced. Although not proven, this could potentially avoid or minimise complications later in life.
Vitamin C has been found to slow down the conversion of homogentisic acid to the polymeric deposits in cartilage and bone. A dose of up to 1g/day is recommended for older children and adults. Nitisinone, an enzyme inhibitor that mediates the formation of homogentisic acid is being used in restricted experimental treatments.
Life expectancy is normal although patients may be at increased risk of heart conditions and may require surgical treatments for spine, hip, knee and shoulder joint problems.
