FECH

Porphyria

More than 110 mutations in the FECH gene have been identified in individuals with a form of porphyria called erythropoietic protoporphyria. A mutation in one copy of the FECH gene reduces each cell's production of ferrochelatase by about half. However, this is not enough to cause the signs and symptoms of porphyria; people with this disorder must also inherit a second altered copy of FECH. In some affected individuals, the second copy of the FECH gene is also nonfunctional, and cells make almost no ferrochelatase. In other affected individuals, the second copy of the FECH gene retains some of its function. This version of the gene is described as a low-expression allele. It reduces, but does not eliminate, the amount of ferrochelatase produced within cells. A combination of two mutated copies of the FECH gene in each cell, or one mutated copy of the gene and one low-expression allele, is necessary for erythropoietic protoporphyria to develop.

A shortage of functional ferrochelatase 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 ferrochelatase 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. High levels of these compounds in the skin cause the oversensitivity to sunlight that is characteristic of this condition. Large amounts of porphyrins in the gallbladder can also cause gallstones. Less commonly, a buildup of these compounds in the liver can result in liver damage.