Learn More - Overview of the Porphyrias
The Cutaneous Porphyrias
Cutaneous porphyrias primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria and X-linked protoporphyria, porphyria cutanea tarda, and hepatoerythropoietic porphyria.
Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP)
What are Erythropoietic Protoporphyria and X-Linked Protoporphyria?
EPP and XLP are both protoporphyrias with similar symptoms and similar biochemical findings, but each is caused by a mutation in a different gene. Some people refer to XLP as a “variant form of EPP”. Symptoms usually first occur in early childhood, and include sun sensitivity, marked by severe pain and swelling of sun-exposed areas, but typically with no blistering or scarring. EPP is caused by a deficiency of the enzyme, ferrochelatase (FECH), whereas XLP is due to an increased activity of another enzyme, aminolevulinic acid-synthase 2 (ALAS2). Both result in significant elevations of protoporphyrins in the liver, sometimes resulting in severe liver complications that are difficult to treat and sometimes require liver transplantation.
Who gets Erythropoietic Protoporphyria and X-Linked Protoporphyria?
EPP and XLP, combined, are the third most common porphyria, with an incidence of possibly 2 to 5 per 1,000,000, and the most common in children. EPP is an autosomal recessive disorder: an affected individual has either (1) a mutation on one of his / her FECH genes and a specific low-expression pre-disposing change (or “alteration”) on the other FECH gene or (2) a mutation on each of his / her FECH genes. XLP is an X-linked disorder, meaning that the disorder-causing gene, ALAS2, is on the X-chromosome (see Genetics 101). Because XLP is X-linked, males and females can both have symptoms, but males are usually more severely affected than females.
What causes Erythropoietic Protoporphyria and X-Linked Protoporphyria?
EPP is caused by a deficiency of the enzyme, ferrochelatase due to mutations in the FECH gene. XLP is caused by over-activity of amino-levulinic acid synthase due to a mutation in the ALAS2 gene. Both result in excess production of protoporphyrin in the bone marrow, transportation to the skin, and collection in the liver.
How is Erythropoietic Protoporphyria and X-Linked Protoporphyria diagnosed?
EPP and XLP are diagnosed by clinicalf symptoms and laboratory tests demonstrating increased protoporphyrin in red blood cells. EPP and XLP are differentiated by the levels of free- and zinc-complexed protoporphyrins: in EPP there is a predominance of free protoporphyrin over zinc protoporphyrin, whereas in XLP, the levels of free and zinc-complexed protoporphyrins are about equal.
- Also see FAQ: What diagnostic tests are available?
What are treatments for Erythropoietic Protoporphyria and X-Linked Protoporphyria?
Treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance but does not lower porphyrin levels. Most patients must learn to avoid sunlight as much as possible. Deficiencies of iron and vitamin D should be prevented. To protect the liver from injury that might precipitate protoporphyric liver failure, Hepatitis A and B vaccinations are recommended, as is the avoidance of alcohol and other hepatotoxins.
Protoporphyric liver failure can appear suddenly and progress rapidly, and is generally treated with a combination of plasmapheresis, blood transfusion, hemin, cholestyramine, vitamin E, and ursodeoxycholic acid, which may reverse or delay liver damage. Levels of porphyrins in plasma and red blood cells should be followed closely during treatment. Liver transplantation is sometimes necessary. It is not yet possible to predict which patients will develop liver failure. Bone marrow transplantation is potentially curative in EPP and can prevent recurrent damage to the transplanted liver.