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Disease Profile

Autosomal erythropoietic protoporphyria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

E80.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Erythrohepatic protoporphyria; EPP; Heme synthetase deficiency;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders;

Summary

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.[1] Inheritance is autosomal recessive.[1][2] 

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.[3][2]

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.[3]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal circulating porphyrin concentration
0010472
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Erythema
0010783
Pruritus
Itching
Itchy skin
Skin itching

[ more ]

0000989
5%-29% of people have these symptoms
Cholelithiasis
Gallstones
0001081
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Decreased liver function
Liver dysfunction
0001410
Eczema
0000964
Edema
Fluid retention
Water retention

[ more ]

0000969
Microcytic anemia
0001935
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Childhood onset
Symptoms begin in childhood
0011463
Hemolytic anemia
0001878
Hepatic failure
Liver failure
0001399
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155

Cause

Erythropoietic protoporphyria is caused by mutations in the FECH gene.[3]

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.[4][2][1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    Management Guidelines

    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
    • The American Porphyria Foundation offers a document that includes information about porphyria, types, testing, and treatment with Panhematin®. Click the "document" link above to view these guidelines.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

      • Afamelanotide(Brand name: Scenesse) Manufactured by Clinuvel Inc.
        FDA-approved indication: October 2019, afamelanotide (Scenesse) was approved to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP).

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

        • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

          Organizations Providing General Support

            Learn more

            These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

            Where to Start

            • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
            • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
            • MedlinePlus Genetics contains information on Autosomal erythropoietic protoporphyria. This website is maintained by the National Library of Medicine.
            • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.

              In-Depth Information

              • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
              • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
              • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
              • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
              • PubMed is a searchable database of medical literature and lists journal articles that discuss Autosomal erythropoietic protoporphyria. Click on the link to view a sample search on this topic.

                References

                1. Poh-Fitzpatrick MB. Protoporphyria. Medscape Reference. 2016; https://emedicine.medscape.com/article/1104061-overview.
                2. Deybach JC, Lecha M, Puy H. Autosomal erythropoietic protoporphyria. Orphanet. July 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=79278.
                3. Balwani M, Bloomer J & Desnick R. Erythropoietic Protoporphyria, Autosomal Recessive. GeneReviews. 2017; https://www.ncbi.nlm.nih.gov/books/NBK100826/.
                4. Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP). American Porphyria Foundation. 2015; https://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/EPP-and-XLP.

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