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Don’t fight Erythropoietic protoporphyria alone.
Find your community on the free RareGuru App.Erythropoietic protoporphyria (EPP) is a type of porphyria. Porphyrias are caused by an abnormality in the heme production process. Heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. Erythropoietic protoporphyria is caused by pathogenic variants (mutations) in the FECH gene which lead to an impaired activity of ferrocheletase (FECH), an important enzyme in heme production. This results in the build-up of protoporphyrin in the bone marrow, red blood cells, blood plasma, skin, and eventually liver. Build up of protoporphyrin can cause extreme sensitivity to sunlight, liver damage, abdominal pain, gallstones, and enlargement of the spleen. Inheritance is autosomal recessive.
Treatment includes avoiding sun and UV light exposure, vitamin D supplements, creams for tanning, and using protective clothing. A medication known as Afamelanotide (Scenesse®), a synthetic α-melanocyte stimulating hormone (a melanocyte is a skin cell that produces melanin, a skin-darkening pigment) analog was approved for treatment of EPP by the European Medicines Agency in 2014 and is awaiting approval in United States by the FDA. This medication increases pain-free sun exposure and has improved quality of life in those with EPP. Liver complications may be treated with cholestyramine and other porphyrin absorbents , plasmapheresis, a procedure where the liquid part of the blood, or plasma, is separated from the blood cells, and intravenous heme are sometimes beneficial. Liver transplantation may be required.
Another type of porphyria, known as X-linked protoporphyria, is caused by a variation in the ALAS2 gene and have similar symptoms to erythropoietic protoporphyria when males are affected by EPP.
Source: GARD Last updated on 05-01-20
In most cases, EPP is caused by mutations in the ferrochelatase ( FECH ) gene. Another type of protoporphyria caused by mutations in the delta-aminolevulinic acid synthase-2 ( ALAS2 ) gene is known as X-linked protoporphyria (XLP). XLP have almost the same symptoms as the EPP in males, but appears to have a higher risk for liver problems than does EPP.
Last updated on 05-01-20
EPP is inherited in an autosomal recessive manner. In most cases, affected individuals have one severe (loss-of-function) mutation that is inherited from one parent, and another weak (low-expression) mutation that is inherited from the other parent. In a small number of cases, an affected individual has two loss-of-function mutations. When 2 carriers of an autosomal recessive condition have children, each child has a:
Last updated on 05-01-20
Erythropoietic protoporphyria is characterized by abnormally high levels of protoporphyrin IX in red blood cells (erythrocytes) and plasma (the fluid part of circulating blood), and by sensitivity to visible light. It is usually first noticed during early childhood and occurs throughout life. Swelling, burning, itching, and redness of the skin may appear during or after exposure to sunlight - even sunlight that passes through a window. The symptoms usually resolve within 12 to 24 hours and heal without significant scarring. In many individuals, the symptoms worsen during the summer months. We were unable to find any information to indicate that skin symptoms grow worse over time.
Last updated on 05-01-20
More than 110 different mutations (changes) in the FECH gene have been identified in individuals with erythropoietic protoporphyria. These mutations may occur in one or both copies of the FECH gene. A single FECH gene mutation greatly reduces the activity of ferrochelatase, but typically does not cause symptoms. Symptoms of erythropoietic protoporphyria are caused by a build-up of porphyrins, chemicals in the body that assist in forming hemoglobin. Excess porphyrins can build up in the skin and other tissues, causing a sensitivity to sunlight, gallstones, and other symptoms related to erythropoietic protoporphyria.
Last updated on 05-01-20
XLP is inherited in an X-linked manner. Women with an ALAS2 mutation have a 50% chance of passing on the disease-causing mutation to each child. Males who are affected transmit the disease-causing mutation to all of their daughters and none of their sons.
Last updated on 05-01-20
DNA studies are important for confirming the diagnosis of EPP and XLP and for the purposes of genetic counseling. Testing should first be done in a person known to have the disease so that the information about the mutation in that individual can be used to guide testing of other family members.
Last updated on 05-01-20
Gene therapy is an experimental technique that uses genes to treat or prevent disease. Gene therapy may allow doctors to treat a disorder by inserting a gene into a patient's cells instead of using medications or surgery. There are several approaches to gene therapy currently being researched including:
Gene therapy is a promising treatment option for a variety of diseases; however, it remains risky and is still under investigation to ensure it is used in a safe and effective manner.
More information about gene therapy is offered by GeneEd, a resource through the National Library of Medicine and the National Human Genome Research Institute. To view, click here.
Last updated on 05-01-20
In EPP caused by FECH mutations, carriers (heterozygotes) and individuals who inherit two low-expression mutations typically do not exhibit symptoms.
Female carriers (heterozygotes) for XLP may develop clinical findings related to the disorder. Symptoms may range from those typically observed in affected males, to being completely symptom-free.
Last updated on 05-01-20
Some individuals with erythropoietic protoporphyria may develop gallstones that contain protoporphyrin. In a small number of cases (5%), high levels of protoporphyrin can lead to liver damage which may progress to a point where transplantation may be necessary.
Last updated on 05-01-20
The FECH gene provides instructions for the production of an enzyme called ferrochelatase. This enzyme is the eighth and the final enzyme involved in the production of heme. Heme is an essential part of iron-containing proteins, including hemoglobin, which carries oxygen in the blood.
Last updated on 05-01-20
Genes are instructions that tell our bodies how to grow, develop, and function. Every person has two copies of each gene, one inherited from each parent.
Last updated on 05-01-20
At this time, gene therapy is not available for people with erythropoietic protoporphyria. Several gene therapy experiments have been carried out in mice with some promising results. We have located several full-text articles that discuss this topic. These articles are listed in PubMed, a searchable database of medical literature.
Fontanellas A, Mendez M, Mazurier F, Cario-Andre M, Navarro S, Ged C, Taine L, Geronimi F, Richard E, Moreau-Gaudry F, Enriquez de Salamanca R, de Verneuil H; Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells. Gene Ther. 2001 Apr; 8(8): 618-26.
Richard E, Mendez M, Mazurier F, Morel C, Costet P, Xia P, Fontanellas A, Geronimi F, Cario-Andre M, Taine L, Ged C, Malik P, de Verneuil H, Moreau- Gaudry F; Gene therapy of a mouse model of protoporphoria with a self- inactiving erythroid-specific lentiviral vector without preselection. Mol Ther. 2001 Oct; 4(4):331-8.
Robert-Richard H, Verneuil de C, Ged L, Taine V, Guyonnet-Dupérat M, Cario- André I, Lamrissi-Garcia Lalanne F, Moreau-Gaudry E. Effective gene therapy of mice with congenital erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells. Am J Hum Genet. 2008 Jan;82(1):113-24.
Last updated on 05-01-20
In the absence of liver failure, people with erythropoietic protoporphyria have normal life expectancies. It is recommended to check the levels of the erythrocyte protoporphyrin (free and zinc-chelated), hematologic indices, and iron profile once a year. Liver function should also be monitored every six to 12 months. Vitamin D 25-OH levels should be monitored in all patients whether or not they are receiving supplements.
Last updated on 05-01-20
Note, these links are external searches against the National Laboratory of Medicine's drug database. You may need to adjust the search if there are no results found.
| Drug Name | Generic Name |
|---|---|
| Scenesse | afamelanotide |
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