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Normal Function
The FECH gene provides instructions for making an enzyme known as ferrochelatase. This enzyme is involved in the production of a molecule called heme. Heme is vital for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is an essential component of iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).
The production of heme is a multi-step process that requires eight different enzymes. Ferrochelatase is responsible for the eighth and final step in this process, in which an iron atom is inserted into the center of protoporphyrin IX (the product of the seventh step) to form heme.
Health Conditions Related to Genetic Changes
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.
More About This Health ConditionOther Names for This Gene
- ferrochelatase (protoporphyria)
- Ferrochelatase, mitochondrial
- Heme Synthetase
- HEMH_HUMAN
- Porphyrin-Metal Chelatase
- Protoheme Ferro-Lyase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. doi: 10.1007/s10545-005-8050-3. Citation on PubMed
- Bloomer JR, Wang Y, Singhal A, Risheg H. Biochemical abnormality in erythropoietic protoporphyria: cause and consequences. J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S36-40. doi: 10.1097/01.mpg.0000226388.56612.fa. Citation on PubMed
- Di Pierro E, Moriondo V, Cappellini MD. Human gene mutations. Gene symbol: FECH. Disease: Porphyria, erythropoietic. Hum Genet. 2004 Jan;114(2):221. No abstract available. Citation on PubMed
- Elder GH. Genetic defects in the porphyrias: types and significance. Clin Dermatol. 1998 Mar-Apr;16(2):225-33. doi: 10.1016/s0738-081x(97)00202-2. No abstract available. Citation on PubMed
- Gouya L, Martin-Schmitt C, Robreau AM, Austerlitz F, Da Silva V, Brun P, Simonin S, Lyoumi S, Grandchamp B, Beaumont C, Puy H, Deybach JC. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. Am J Hum Genet. 2006 Jan;78(1):2-14. doi: 10.1086/498620. Epub 2005 Nov 15. Citation on PubMed or Free article on PubMed Central
- Gouya L, Puy H, Robreau AM, Bourgeois M, Lamoril J, Da Silva V, Grandchamp B, Deybach JC. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet. 2002 Jan;30(1):27-8. doi: 10.1038/ng809. Epub 2001 Dec 20. Citation on PubMed
- Gouya L, Puy H, Robreau AM, Lyoumi S, Lamoril J, Da Silva V, Grandchamp B, Deybach JC. Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias. Hum Genet. 2004 Feb;114(3):256-62. doi: 10.1007/s00439-003-1059-5. Epub 2003 Dec 11. Citation on PubMed
- Herrero C, To-Figueras J, Badenas C, Mendez M, Serrano P, Enriquez-Salamanca R, Lecha M. Clinical, biochemical, and genetic study of 11 patients with erythropoietic protoporphyria including one with homozygous disease. Arch Dermatol. 2007 Sep;143(9):1125-9. doi: 10.1001/archderm.143.9.1125. Citation on PubMed
- Kauppinen R. Porphyrias. Lancet. 2005 Jan 15-21;365(9455):241-52. doi: 10.1016/S0140-6736(05)17744-7. Citation on PubMed
- Rand EB, Bunin N, Cochran W, Ruchelli E, Olthoff KM, Bloomer JR. Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria. Pediatrics. 2006 Dec;118(6):e1896-9. doi: 10.1542/peds.2006-0833. Epub 2006 Oct 30. Citation on PubMed
- Risheg H, Chen FP, Bloomer JR. Genotypic determinants of phenotype in North American patients with erythropoietic protoporphyria. Mol Genet Metab. 2003 Sep-Oct;80(1-2):196-206. doi: 10.1016/j.ymgme.2003.07.001. Citation on PubMed
- Sassa S, Kappas A. Molecular aspects of the inherited porphyrias. J Intern Med. 2000 Feb;247(2):169-78. doi: 10.1046/j.1365-2796.2000.00618.x. Citation on PubMed
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