

Erythropoietic Protoporphyria (EPP) is a rare inherited metabolic disorder characterized by a deficiency of the enzyme ferrochelatase (FECH). Due to abnormally low levels of this enzyme, excessive amounts of protoporphyrin accumulate in the bone marrow, blood plasma, and red blood cells. Protoporphyrin is excreted by the liver into the bile, after which it enters the intestine and is excreted in the feces. It is not soluble in water so is not excreted in the urine. The major symptom of this disorder is hypersensitivity of the skin to sunlight and some types of artificial light, such as fluorescent lights (photosensitivity). After exposure to light, the skin may become itchy and red. Affected individuals may also experience a burning sensation on their skin. The hands, arms, and face are the most commonly affected areas. Some people with Erythropoietic Protoporphyria may also have complications related to liver and gallbladder function.


EPP and XLP, combined, are the third most common Porphyria, with an incidence of possibly 2 to 5 per 1,000,000. They are the most common Porphyria in children. EPP is caused by a lack of the enzyme, ferrochelatase due to mutations in the FECH gene.

Erythropoietic Protoporphyria affects males and females in equal numbers. It is estimated that the disorder occurs in about 1 in about 74,300 individuals. The onset of symptoms affecting the skin usually occurs in infancy; however, in some cases, onset may not occur until adolescence or adulthood.

X-linked Protoporphyria affects males and females. However, males usually develop a severe form of the disorder while females with an ALAS2 mutation may range from having no symptoms (asymptomatic) to developing a severe form of the disorder. The exact incidence or prevalence of X-linked Protoporphyria is unknown. The disorder has only been reported in the medical literature in a handful of families in Europe, South Africa and Japan.


Synonyms of Erythropoietic Protoporphyria

  • EPP
  • Erythrohepatic Protoporphyria
  • Protoporphyria

Synonyms of X-Linked Protoporphyria

  • X-linked dominant Protoporphyria
  • XLP


Erythropoietic Protoporphyria is a rare disorder inherited as an autosomal dominant genetic trait with poor penetrance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.




The symptoms of Erythropoietic Protoporphyria develop due to excessive levels of a chemical called protoporphyrin that accumulates in certain tissues of the body (i.e., the plasma, red blood cells, and the liver). Excessive protoporphyrin levels occur as the result of abnormally low levels of the enzyme ferrochelatase (FECH).

Signs and Symptoms


The most common symptom of Erythropoietic Protoporphyria is hypersensitivity of the skin to sunlight and some types of artificial light (photosensitivity), with pain, itching, and/or burning of the skin occurring after exposure to sunlight and occasionally to fluorescent light. Affected individuals may also exhibit abnormal accumulations of body fluid under affected areas (edema) and/or persistent redness or inflammation of the skin (erythema). In rare cases, affected areas of the skin may develop sac-like lesions (vesicles or bullae), scar, and/or become discolored (hyperpigmentation) if exposure to sunlight is prolonged. However, scarring and/or discoloring of the skin is uncommon and rarely severe. These affected areas of skin may become abnormally thick. In addition, in some cases, affected individuals may also exhibit malformations of the nails. The severity and degree of photosensitivity is different from case to case. Photosensitivity is often seen during infancy; however, in some cases, it may not occur until adolescence or adulthood.

In some affected individuals, the flow of bile through the gallbladder and bile ducts (biliary system) may be interrupted (cholestasis) causing gallstones (cholelithiasis) to form. In turn, such stones can cause obstruction and/or inflammation of the gallbladder (cholecystitis). Rarely, affected individuals may also develop liver damage that, in very severe cases, may lead to liver failure requiring transplantation.

Symptoms usually start in childhood, but diagnosis is often delayed since blistering is not common and, because the porphyrins are insoluble, they usually escape detection on urinanalysis. The diagnosis is made upon finding increased levels of the protoporphyrin in the plasma or red blood cells.




  • Mayo Medical Laboratories, 1-800-533-1710

Porphyrins are almost always elevated in plasma in EPP but may be normal in mild cases. Fecal porphyrins may be normal or increased.

A diagnosis of X-linked protoporphyria may be made through blood tests that can detect markedly increased levels of metal-free and zinc-bound protoporphyrins within red blood cells (erythrocytes). A higher ratio of zinc-bound protoporphyrin to metal-free protoporphyrin can differentiate X-linked protoporphyria from EPP.

Molecular genetic testing can confirm a diagnosis of X-linked protoporphyria by detecting mutations in the ALAS2 gene (the only gene known to cause this disorder).




The diagnosis of Erythropoietic Protoporphyria (EPP) may be made by a thorough clinical evaluation, characteristic physical findings, and specialized laboratory tests. EPP is usually diagnosed during infancy or early childhood, due to characteristic skin symptoms. The diagnosis may be confirmed by testing the red blood cells (erythrocytes) for increased levels of protoporphyrin.


Sunlight protection



Other considerations


Yearly monitoring. Testing to include erythrocyte total protoporphyrin, plasma porphyrin, complete blood counts, ferritin and liver function tests should be done yearly. Porphyrin levels are expected to be stable and liver tests to remain normal. EPP patients may have evidence of iron deficiency, and an iron supplement may be advisable if the serum ferritin is below about 20 ng/mL.




Drugs. Drugs that are harmful in other Porphyrias are not known to make EPP worse but are best avoided as a precaution. This may include estrogens and other drugs that might reduce bile formation. A short course of a non-steroidal anti-inflammatory drug can provide some pain relief after an episode of photosensitivity but can cause ulcerations of the digestive track especially with prolonged use.


Children with EPP. Please see the Shadow Jumpers area of this website.

Beta-Carotene. In Erythropoietic Protoporphyria, a high potency form of oral beta-carotene (Lumitene, Tishcon) may be given to improve an affected individual's tolerance of sunlight. In some cases, the drug cholestyramine may be given to alleviate skin symptoms and lower the protoporphyrin levels in the body.

Iron. When iron deficiency is present, iron supplements may be given.


Investigational Therapies


See Member Stories on Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP)