Alkaptonuria is one of 4 disorders originally defined as an inborn error of metabolism. The hallmark of the disease is passage of urine that becomes black when left standing. There is a familial pattern of inheritance. The defect lies in the catabolic pathway of tyrosine. The product, homogentisic acid, in deficiency of the hepatic enzyme homogentisate 1,2- dioxygenase (HGO) accumulates in the blood, but is rapidly cleared in the kidney and excreted. Upon contact with air, homogentisic acid is oxidized to form a pigmentlike polymeric material responsible for the black color of standing urine. Although homogentisic acid blood levels are kept very low through rapid kidney clearance, over time homogentisic acid is deposited in cartilage throughout the body and is converted to the pigmentlike polymer through an enzyme-mediated reaction that occurs chiefly in collagenous tissues. As the polymer accumulates within cartilage, a process that takes many years, the normally transparent tissues become slate blue, an effect ordinarily not seen until adulthood. The earliest sign of the disorder is the tendency for diapers to stain black.. but in most cases desease is hardly diagnosed before the fourth decade of life, external signs of pigment deposition, called ochronosis, begin to appear. The slate blue, gray, or black discoloration of sclerae and ear cartilage is indicative of widespread staining of the body tissues, particularly cartilage. The hips, knees, and intervertebral joints are affected most commonly and show clinical symptoms resembling rheumatoid arthritis. Because of calcifications that occur in these sites, however, the radiologic picture is more consistent with osteoarthritis.

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