UROS

Porphyria

More than 35 mutations in the UROS gene have been found to cause a form of porphyria known as congenital erythropoietic porphyria. Most of these mutations change single protein building blocks (amino acids) in uroporphyrinogen III synthase. The most common UROS gene mutation, which is found in about one-third of all cases of congenital erythropoietic porphyria, replaces the amino acid cysteine with the amino acid arginine at position 73 (written as Cys73Arg or C73R). Several other mutations occur in a nearby region of DNA that regulates the activity of the UROS gene.

Mutations in or near the UROS gene alter the structure and function of uroporphyrinogen III synthase, which reduces the enzyme's activity. A shortage of functional uroporphyrinogen III synthase allows compounds called porphyrins to build up in developing red blood cells. These compounds are formed during the normal process of heme production, but reduced activity of uroporphyrinogen III synthase allows them to accumulate to toxic levels. The excess porphyrins can leak out of developing red blood cells and be transported through the bloodstream to the skin and other tissues. An accumulation of these substances in the skin causes oversensitivity to sunlight and the other characteristic features of congenital erythropoietic porphyria.