Congenital Erythropoietic Porphyria (CEP)
What is Congenital Erythropoietic Porphyria (CEP)?
Congenital Erythropoietic Porphyria (CEP), also known as Günther's disease, is a rare genetic disorder affecting the heme biosynthesis pathway due to a deficiency of the enzyme uroporphyrinogen III synthase (UROS). Porphyrins are precursor compounds used to make heme, a component of hemoglobin, the oxygen carrying protein in red blood cells. The enzyme deficiency leads to the accumulation of porphyrins, particularly uroporphyrin and coproporphyrin, resulting in a variety of symptoms primarily affecting the skin and the blood.
Synonyms
- Erythropoietic uroporphyria
- Gunthers Disease
- Uroporphyrinogen III synthase deficiency
Congenital Erythropoietic Porphyria (CEP), also known as Günther's disease, is a rare genetic disorder affecting the heme biosynthesis pathway due to a deficiency of the enzyme uroporphyrinogen III synthase (UROS). Porphyrins are precursor compounds used to make heme, a component of hemoglobin, the oxygen carrying protein in red blood cells. The enzyme deficiency leads to the accumulation of porphyrins, particularly uroporphyrin and coproporphyrin, resulting in a variety of symptoms primarily affecting the skin and the blood.
CEP is extremely rare, with an estimated prevalence ranging from 1 in 1,000,000 to 1 in 2,000,000 individuals globally. Over 200 cases have been documented, and the condition is more prevalent in certain populations, especially where consanguineous marriages between related individuals occur.
| Name | Abbreviation |
|---|---|
| Erythropoietic uroporphyria | |
| Gunthers Disease | |
| Uroporphyrinogen III synthase deficiency |
CEP is caused by mutations in the UROS gene located on chromosome 10. This gene encodes the enzyme responsible for the conversion of uroporphyrinogen I to uroporphyrinogen III. The mutations are inherited in an autosomal recessive pattern, meaning both copies of the gene must be mutated for the disorder to manifest. (See RareShare Guide on Genetic Inheritance.)
Symptoms
Symptoms usually appear in early childhood and can include:
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Photosensitivity: Severe skin reactions, such as blistering and scarring upon sun exposure.
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Anemia: Hemolytic anemia due to the destruction of red blood cells.
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Skeletal deformities: Bone abnormalities due to bone marrow expansion.
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Dental abnormalities: Red-brown discoloration of teeth (erythrodontia).
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Splenomegaly: Enlargement of the spleen.
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Hypertrichosis: Increased hair growth on sun-exposed skin.
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Urine discoloration: Reddish or brown urine, especially upon exposure to light.
Growth retardation: Delayed growth in severe cases.
The diagnosis of CEP involves:
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Clinical Evaluation: Assessing symptoms and family history.
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Biochemical Tests: Measuring elevated porphyrin levels in urine, blood, and stool.
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Genetic Testing: Identifying mutations in the UROS gene.
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Enzyme Activity Assays: Measuring UROS enzyme function.
Skin Biopsy: May show changes consistent with porphyria.
There is no cure for CEP; management focuses on alleviating symptoms and preventing complications:
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Sun Protection: Wearing protective clothing, using high-SPF sunscreens, and avoiding direct sunlight.
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Blood Transfusions: To manage severe anemia.
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Splenectomy: Surgical removal of the spleen in severe cases.
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Oral Beta-Carotene: To improve sun tolerance.
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Hydroxychloroquine: May be used to reduce porphyrin production.
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Bone Marrow Transplantation: In severe cases, this can be potentially curative.
Gene Therapy: Currently under investigation.
The prognosis for individuals with CEP varies widely. While many can manage their symptoms effectively and lead relatively normal lives, severe cases can lead to significant disfigurement, chronic anemia, and other complications, impacting quality of life and life expectancy. Early diagnosis and intervention are essential for better outcomes.
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Puy, H., et al. (2010). "Porphyrias: A review." The Lancet, 375(9723), 1167-1177.
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Balwani M, Desnick RJ. (2023). "Congenital erythropoietic porphyria." In: GeneReviews®. Seattle (WA): University of Washington.
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Fritsch C, et al. (1997). "Congenital erythropoietic porphyria." Journal of the American Academy of Dermatology, 36(4), 594-610.
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Katugampola RP, et al. (2012). "A management algorithm for congenital erythropoietic porphyria." British Journal of Dermatology, 167(4), 888-900.
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Erwin AL, Desnick RJ. (2019). "Congenital erythropoietic porphyria: Recent advances." Molecular Genetics and Metabolism, 128(3), 288-297.
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Clinical Trials
CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access.
Enrolling is easy.
- Complete the screening form.
- Review the informed consent.
- Answer the permission and data sharing questions.
After these steps, the enrollment process is complete. All other questions are voluntary. However, these questions are important to patients and their families to create awareness as well as to researchers to study rare diseases. This is why we ask our participants to update their information annually or anytime changes to their information occur.
Researchers can contact CoRDS to determine if the registry contains participants with the rare disease they are researching. If the researcher determines there is a sufficient number of participants or data on the rare disease of interest within the registry, the researcher can apply for access. Upon approval from the CoRDS Scientific Advisory Board, CoRDS staff will reach out to participants on behalf of the researcher. It is then up to the participant to determine if they would like to join the study.
Visit sanfordresearch.org/CoRDS to enroll.
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