Alkaptonuria is a rare genetic disorder caused by a deficiency of the enzyme homogentisate 1,2-dioxygenase (HGD). This enzyme is responsible for the breakdown of an amino acid called phenylalanine and a related compound called tyrosine. In individuals with alkaptonuria, the HGD enzyme is either absent or not functioning properly, leading to a buildup of a substance called homogentisic acid.
The accumulation of homogentisic acid in the body results in a condition called ochronosis, which causes the darkening of tissues such as cartilage, connective tissues, and certain organs. The urine of individuals with alkaptonuria turns dark upon exposure to air due to the presence of homogentisic acid.
Alkaptonuria is an autosomal recessive disorder, which means that an affected individual inherits two copies of the defective gene, one from each parent. The HGD gene, located on chromosome 3, carries the instructions for producing the HGD enzyme. Mutations in this gene disrupt the production or function of the enzyme, leading to alkaptonuria.
