Erythropoietic protoporphyria is a type of porphyria. Porphyrias are caused by an abnormality in the heme production process. Heme is essential in enabling our blood cells to carry oxygen and in breaking down chemical compounds in the liver. Erythropoietic protoporphyria is caused by impaired activity of ferrocheletase (FECH), an important enzyme in heme production. This results in the build-up of protoporphyrin in the bone marrow, red blood cells, blood plasma, skin, and eventually liver. Build up of protoporphyrin can cause extreme sensitivity to sunlight, liver damage, abdominal pain, gallstones, and enlargement of the spleen.
- Cutaneous photosensitivity
Symptoms can usually be managed by the simple expedient of limiting sun exposure. Protective clothing is also very helpful; however, since the photosensitivity results from light in the visible spectrum, most sunscreens (with the exception of light-reflecting substances such as zinc oxide) are of little use.
Erythropoietic protoporphyria is caused by mutations in the FECH gene.
EPP is inherited in an autosomal recessive manner. In most cases, affected individuals have one severe (loss-of-function) mutation that is inherited from one parent, and another weak (low-expression) mutation that is inherited from the other parent. In a small number of cases, an affected individual has two loss-of-function mutations. When 2 carriers of an autosomal recessive condition have children, each child has a:
- 25% (1 in 4) chance to be affected
- 50% (1 in 2) chance to be an unaffected carrier like each parent
- 25% (1 in 4) chance to be unaffected and not be a carrier
More than 125 different mutations of the ferrochelatase gene have been identified to date. Loss of ferrochelatase activity by as much as 50% as the result of 1 mutant gene is generally insufficient to cause overt disease when its complementary allele has normal function. Ferrochelatase genotypes composed of either 2 mutant alleles (~4% of cases) or 1 mutation and a nonmutant allele with a specific intronic polymorphism (~95% of cases) have been found in most symptomatic individuals. This polymorphism enhances aberrant splicing and rapid degradation of ferrochelatase mRNA with resultant low expression. The pairing of a mutated allele encoding a severely impaired enzyme protein with a low-expressing normal variant allele typically yields total residual enzyme activity less than 30% of normal, low enough to cause protoporphyrin accumulation.
EPP is generally suspected by the presence of acute photosensitivity of the skin and can be confirmed by detection of a plasmatic fluorescence peak at 634 nm. It is also useful to find increased levels of protoporphyrin in feces and the demonstration of an excess of free protoporphyrin in erythrocytes.
Screening for FECH mutation on one allele or aminolevulinic acid synthase 2 gain-of-function mutation in selected family members may be useful, especially in genetic counseling.
Liver biopsy confirms hepatic disease in EPP by the presence of protoporphyrin deposits in the hepatocytes that can be observed as a brown pigment within the biliary canaliculi and the portal macrophages. Macroscopically, the cirrhotic liver can have a black color due to protoporphyrin deposits. Using polarized light the characteristic Maltese cross shape of birefringent crystalline pigment deposits is found. The examination of liver tissue under a Wood's lamp reveals a red fluorescence due to protoporphyrin. Liver biopsy is not helpful for estimation of prognosis of liver disease.
In the absence of liver failure, individuals with erythropoietic protoporphyria have normal life expectancies. Porphyrias are life-long diseases with symptoms that come and go. Some forms of the disease cause more symptoms than others. Proper treatment and avoidance of triggers can help prolong the time between attacks.
There is no cure for this disorder; however, symptoms can usually be managed by limiting exposure to daytime sun and fluorescent lights. Protective clothing is also very helpful. Since the photosensitivity results from light in the visible spectrum, most sunscreens (with the exception of light-reflecting substances such as zinc oxide) are of little use. Some individuals may decrease their sun sensitivity with daily doses of beta carotene, though a recent meta analysis of carotene treatment has called its effectiveness into question. Some patients gradually build a protective layer of melanin by regularly exposing themselves for short times to ultraviolet radiation.
Window films which block UV and visible light up to 450 nm can provide relief from symptoms if applied to the patient's automobile and home windows.
EPP is considered one of the least severe of the porphyrias. Unless there is liver failure, it is not a life-threatening disease.