Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within minutes of sun/light exposure and may be accompanied by swelling and redness. Vesicular lesions are uncommon. Symptoms, which may seem out of proportion to the visible skin lesions, may persist for hours or days after the initial phototoxic reaction. Photosensitivity usually remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy, similar to that seen in the acute porphyrias. Except for the small minority with advanced liver disease, life expectancy is not reduced.
Detection of markedly increased free erythrocyte protoporphyrin is the most sensitive and specific biochemical diagnostic test for EPP. Identification of biallelic mutations in FECH, encoding ferrochelatase, confirms the diagnosis.
EPP is inherited in an autosomal recessive manner. In 90%-95% of cases an affected individual inherits a loss-of-function FECH allele from one parent and a low-expression FECH allele from the other parent. In about 5%-10% of cases, an affected individual has two loss-of-function FECH alleles. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) and individuals who inherit two low-expression alleles are asymptomatic. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family have been identified.