UROD

The UROD gene provides instructions for the production of an enzyme called uroporphyrinogen decarboxylase. This enzyme is responsible for the fifth step in the production of heme, the iron-containing part of hemoglobin. Hemoglobin is the oxygen-carrying protein in red blood cells. Each step in heme production is controlled by a different enzyme, each of which is produced from a single gene. Uroporphyrinogen decarboxylase removes carbon and oxygen from uroporphyrinogen III (the product of the fourth step in the production of heme) to form coproporphyrinogen III. Three additional enzymes modify this product before it becomes heme. The heme molecule is then incorporated into hemoglobin and packaged into red blood cells, or it is used in the liver for the production of certain liver enzymes.

porphyria - caused by mutations in the UROD gene

Approximately 50 mutations that cause a form of porphyria called porphyria cutanea tarda have been identified in the UROD gene. These mutations occur in one of the two copies of the UROD gene in each cell, which usually reduces the activity of uroporphyrinogen decarboxylase by 50 percent throughout the body. (In rare cases, the enzyme's activity is reduced only in the liver.) As a result, byproducts of heme production called porphyrins build up in the body, particularly in the liver. This buildup, in combination with nongenetic factors (such as alcohol, smoking, certain hormones, excess iron, and viral infections), causes this type of porphyria.

At least 10 mutations in the UROD gene have been identified in families with another type of porphyria, hepatoerythropoietic porphyria. Most of these mutations are unique to this type of porphyria and have not been found in porphyria cutanea tarda. Mutations that cause hepatoerythropoietic porphyria occur in both copies of the UROD gene in each cell, which reduces the activity of uroporphyrinogen decarboxylase to less than 10 percent of normal. Extremely low levels of this enzyme prevent sufficient amounts of heme from being produced. As a result, byproducts of heme production called porphyrins build up in the body, causing this type of porphyria.