Phenylketonuria :    • Phenylketonuria  and its metabolism  
Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase if a person inherits an abnormal copy from both parents (it is a recessive condition), the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidized form alkapton are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves, as well as precipitating as kidney stones and stones in other organs.
Patients with alkaptonuria are asymptomatic as children or young adults, but their urine may turn brown or even inky black if collected and left exposed to open air. Pigmentation may be noted in the cartilage of the ear and other cartilage, and the sclera and corneal limbus of the eye.
All people carry in their DNA two copies (one received from each parent) of the gene HGD, which contains the genetic information to produce the enzyme homogentisate 1,2-dioxygenase (HGD) which can normally be found in numerous tissues in the body (liver, kidney, small intestine, colon, and prostate).
If the diagnosis of alkaptonuria is suspected, it can be confirmed or excluded by collecting urine for 24 hours and determining the amount of homogentisic acid by means of chromatography. No assay of HGA in blood has been validated.[1] The Genetic Testing Registry is used for maintaining information about the genetic test for alkaptonuria.