Alkaptonuria (AKU) is a rare genetic disorder caused by mutations in the homogentisic acid oxidase (HGO) gene. The HGO gene is responsible for producing an enzyme called homogentisic acid oxidase, which is used to break down the amino acids tyrosine and phenylalanine. In individuals with AKU, this enzyme is not produced or is produced in insufficient quantities leading to an accumulation of homogentisic acid in the blood and urine.
The accumulation of homogentisic acid in the body causes a wide range of symptoms, including osteoarthritis-like joint pain, darkening of urine, and a bluish-black discoloration of the skin, nails, and sclerae. Over time, this discoloration will turn brown and the affected tissues will become brittle and dry. Additionally, individuals with AKU are at increased risk of developing kidney stones and urolithiasis.
The cause of AKU is a mutation in the HGO gene which leads to a deficiency in the enzyme homogentisic acid oxidase. This mutation is typically inherited in an autosomal recessive pattern, meaning that both parents must carry the gene for it to be passed on to their children.
The diagnosis of AKU is typically made through urine testing, which can detect the presence of homogentisic acid. Genetic testing may also be used to confirm the diagnosis. Treatment typically consists of dietary changes and medications to reduce the production of homogentisic acid. In some cases, surgical treatments may be necessary to reduce joint pain.