An Overview of Erythropoietic Protoporphyria

Erythropoietic protoporphyria (EPP) is one of several rare inherited disorders called porphyrias. Patients with EPP have mutations in one or more genes that cause them to have decreased activity of an enzyme called protoporphyrin IX in their red blood cells. This leads to a buildup of a protein called protoporphyrin that can make their skin very sensitive to sunlight.

Patients with EPP can experience severe pain when they are in the sun or even exposed to some intense artificial lighting. These symptoms usually begin in childhood and persist throughout a patient’s life. EPP is the third most common porphyria—estimated to occur in about 1 in about 74,300 individuals—and the type most often seen in children. Women and men appear to be equally affected. While there is currently no known cure for EPP, there are ways to manage it.

The most common symptom of EPP is photosensitivity, which means a person experiences pain or other skin symptoms when they are in the sun. Photosensitivity caused by EPP can be so severe that patients experience pain even when exposed to sunlight coming through the windows of a car they're driving or riding in.

Patients may also have other skin symptoms after they've been exposed to sunlight, including: 

• Itching
• Burning
• Swelling

Pain and other symptoms are felt most often on the face, hands, and arms. Patients often notice the symptoms happen more frequently in the summer. These symptoms can range from being mild annoyances to severe and debilitating in their day-to-day lives. 

Symptoms usually go away within 24 hours. Patients with EPP usually do not experience any lasting skin damage, like scarring (though blisters and scars can result from other types of porphyrias that affect the skin).

Some patients with EPP may also experience liver damage, as having too much protoporphyrin in the body can put stress on the liver. It is rare to have severe liver damage from EPP, however—this complication occurs in less than 5 percent of patients. Some patients with EPP (up to 8 percent) may also experience gallstones that have protoporphyrin in them, which can lead to gallbladder inflammation (cholecystitis).

EPP is most often caused by mutations in the ferrochelatase gene (FECH). Less frequently, EPP is caused by mutations in another gene called delta-aminolevulinic acid synthase-2 gene (/ALAS2/). When this gene causes the condition, it's referred to as X-linked protoporphyria (XLP). 

The mutations in the FECH gene are passed down in a pattern called autosomal recessive. This means that one parent has a very strong mutation and the other has a weaker one. A child receives both mutations, but the stronger mutation dominates the weaker one. The parent who has the strong mutation won’t have symptoms unless they also have a weaker mutation from one of their parents. If they don’t have symptoms, they are what’s called a “carrier." This means that even though they don’t show symptoms of the disease, they can pass the gene that causes it on to their child.

Inheriting these mutations in the FECH gene causes a patient to have too much protoporphyrin IX in their red blood cells and plasma. The protoporphyrin builds up in the bone marrow, the blood cells, and the liver.

Symptoms related to sunlight exposure typically appear in childhood—even in infancy—but it may take time to get diagnosed with EPP. Children may lack the language to express they are in pain. If they have no visible skin symptoms, it can be difficult for parents or doctors to make the connection. EPP is also a very rare condition. As a result, many pediatricians and general practitioners may not be familiar with it.

Once a doctor suspects a patient has EPP, it is very easy to test for it and confirm the diagnosis. There are several tests to detect abnormal levels of protoporphyrin in the blood, urine, and feces.

Additionally, genetic testing may reveal the specific mutations in the FECH gene. This can be very important information for patients, as they may want to seek genetic counseling when they begin thinking about family planning. 

If one family member is found to have EPP, it is not uncommon for other members of the family to be tested to see if they carry a mutation as well, even if they aren’t showing symptoms. 

The most important treatment for patients with EPP is sun protection. Avoiding or limiting sunlight exposure, as well as any exposure to some forms of fluorescent light, is the best way to prevent and control symptoms. 

Examples of sunlight protection can include:

• Wearing hats when outside
• Wearing clothes that cover as much skin as possible (long sleeves and pants) 
• Sunscreen
• Sunglasses
• Tinting windows at home and in vehicles 
• For some patients, certain drugs or supplements (such as oral beta-carotene) may be prescribed by a doctor to help improve sunlight tolerance. 

Patients with EPP may be advised to avoid certain medications or supplements, such as estrogen-containing birth control pills or hormone replacement therapy, testosterone supplements, or any drugs that have certain effects on the liver. For this reason, patients may also be advised not to drink alcohol.

When patients with EPP undergo surgery, there may need to be special considerations regarding anesthesia. Patients may also need extra protection during surgery to avoid symptoms after being exposed to the strong overhead lighting used in operating rooms.

For patients with EPP, having to avoid sunlight can have a negative impact on quality of life, especially in terms of social experiences. This may especially be true for children and young adults, who may feel left out of social activities and special occasions such as summer vacations, school trips, and birthday parties.

Resources like Camp Discovery provide opportunities for children and their families. Additionally, the Guest Relations departments of Disneyland and Disney World are also able to make accommodations for families and children with EPP so they can enjoy many special childhood experiences and take part in activities outside with their peers.