EPP is a rare condition, with an estimated prevalence of 1 in 75,000 to 1 in 200,000 individuals worldwide. EPP is considered the most common type of erythropoietic porphyria, diagnosed in childhood after the onset of photosensitivity symptoms. It occurs equally in males and females, except in cases of X-linked protoporphyria (XLPP), which mostly affects males. The exact prevalence of X-linked protoporphyria is unknown as the disorder has only been reported in the medical literature in a handful of families in Europe, South Africa and Japan.

The underlying cause of the more common form of EPP is a genetic mutation in the FECH gene, which encodes the enzyme ferrochelatase. This enzyme is involved in the final step of heme synthesis. Mutations in FECH lead to a functional deficiency in ferrochelatase, causing protoporphyrin IX to accumulate. This form of EPP is inherited in an autosomal recessive pattern (see RareShare Guide on Genetic Inheritance).

In X-linked protoporphyria (XLPP), the cause is a mutation in the ALAS2 gene located on the X-chromosome. The ALAS2 gene encodes a protein enzyme known as erythroid specific 5-aminolevulinate synthase 2. Mutations result in increased enzymatic activity and overproduction of protoporphyrin IX, leading to accumulation of this molecule and EPP-like symptoms. This form of EPP is inherited in a X-linked pattern (see RareShare Guide on Genetic Inheritance).  

The symptoms of EPP are primarily cutaneous (skin-related) and hepatic (liver-related), though some systemic symptoms can also occur.

Cutaneous Symptoms:

• Severe photosensitivity: Immediate, painful reactions upon exposure to sunlight or bright artificial light.

• Burning, redness, swelling, and blistering of the skin (in more severe cases).

• Itching or tingling sensations after light exposure.

• Chronic sun exposure can lead to scarring, hyperpigmentation, and thickened, wax-like skin, particularly on sun-exposed areas such as the face, hands, and neck.

Hepatic Symptoms:

• Liver dysfunction occurs in about 5-20% of individuals, potentially causing:

  • Cholestatic liver disease (disruption in bile flow)

  • Gallstones

  • Jaundice (yellowing of the skin and eyes)

  • Hepatomegaly (enlarged liver)

• In severe cases, liver failure may develop, which could require a liver transplant.

Other Symptoms:

• Fatigue and weakness, often due to mild anemia.

• Abdominal pain, which may be related to liver complications.

• Neurological symptoms are rare but can occur in some patients.

• Developmental delay may be observed in children with severe liver involvement.

The diagnosis of Erythropoietic Protoporphyria is based on a combination of clinical features, laboratory tests and genetic analysis.

Clinical Diagnosis:

• Photosensitivity is a key diagnostic feature, with skin reactions after light exposure.

• Liver symptoms (e.g., jaundice, hepatomegaly) may also raise suspicion, especially in severe cases.

• Family history.

Laboratory Tests:

1. Protoporphyrin Levels:

   • Elevated levels of free protoporphyrin in red blood cells and plasma are indicative of EPP.

   • Plasma fluorescence peak at 634 nm.

2. Ferrochelatase Activity:

   • Decreased activity of the ferrochelatase enzyme, measured in erythrocytes or cultured skin fibroblasts.

3. Genetic Testing:

   • Mutations in the FECH gene can be detected via genetic testing.

   • ALAS2 gene mutations may be identified in cases of X-linked protoporphyria.

4. Liver Function Tests:

   • Elevated levels of liver enzymes (e.g., ALT, AST) may indicate liver involvement.

5. Imaging Studies:

   • Ultrasound or MRI of the liver may be used to evaluate for liver enlargement or signs of damage.

6. Additional Tests:

   • Complete blood counts, iron studies and zinc protoporphyrin levels.

There is no cure for Erythropoietic Protoporphyria, but the condition can be managed through lifestyle modifications, medications and in some cases, surgical interventions.

Sun Protection:

• Avoidance of sunlight: The primary treatment involves minimizing exposure to sunlight and bright artificial light.

• Protective Clothing: Wearing UV-blocking clothing, gloves, wide-brimmed hats, and sunglasses.

• Sunscreens: Use of physical sunscreens (e.g., zinc oxide) that block UV light is essential.

Medications:

• Beta-carotene: Oral beta-carotene supplementation may reduce photosensitivity by increasing the skin's tolerance to sunlight.

• Vitamin D supplementation.

• Afamelanotide (Scenesse): An α-melanocyte-stimulating hormone analogue that increases melanin production in the skin, providing better protection against UV radiation.

• Liver Protection: For liver involvement, medications like ursodeoxycholic acid may be used to protect liver function.

Advanced Treatments:

• Liver Transplantation: In cases of severe liver disease, a liver transplant may be necessary.

• Blood transfusions or plasmapheresis.

• Bone Marrow Transplantation: In rare, severe cases, bone marrow transplant may be considered to address underlying metabolic issues.

Supportive Care:

• Regular monitoring of liver function and protoporphyrin levels.

• Pain management: For skin reactions, anti-inflammatory or topical steroids may be used.

The prognosis for individuals with Erythropoietic Protoporphyria depends on the severity of symptoms, particularly liver involvement.

• Skin Symptoms: With proper sun protection, many individuals with EPP can live relatively normal lives. Chronic photosensitivity can be managed effectively with avoidance of sunlight and use of protective measures.

• Liver Involvement: A small percentage (5-20%) may develop severe liver complications. Liver failure, though rare, may require a liver transplant.

• Lifespan: The lifespan is typically normal for most individuals with EPP, though the condition may impact quality of life due to limitations on outdoor activities and the need for constant sun protection.

Many patients are able to manage their condition through lifestyle adjustments and sun protection. However, quality of life can be significantly impacted due to the limitations on outdoor activities. 

1. Lecha, M., et al. (2009). “Erythropoietic protoporphyria.” Orphanet Journal of Rare Diseases, 4, 19.

2. Balwani, M., et al. (2019). “The porphyrias: advances in diagnosis and treatment.” Blood, 133(7), 733-741.

3. Langendonk, J. G., et al. (2015). “Afamelanotide for Erythropoietic Protoporphyria.” New England Journal of Medicine, 373(1), 48-59.

4. Holme, S. A., et al. (2006). “Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life.” British Journal of Dermatology, 155(3), 574-581.

5. Erythropoietic protoporphyria and X-linked protoporphyria. (n.d.) NORD (National Organization for Rare Disorders). Erythropoietic protoporphyria and X-linked protoporphyria.