Erythropoietic Protoporphyria

Also known as EPP

Erythropoietic Protoporphyria

There are approximately 20 families with erythropoietic protoporphyria in South Africa. This is the commonest erythropoietic form of porphyria—one in which it is predominantly erythroid haem synthesis which is disturbed.
Enzyme Defect
The defective enzyme is ferrochelatase, which is responsible for the insertion of iron into protoporphyrin to form haem (See Introduction to porphyria). Large amounts of protoporphyrin accumulate in erythrocytes (which will fluoresce under ultraviolet light), plasma and in severe cases, in hepatocytes.

Gene Defect
The inheritance is complex. The basic trait is transmitted as an autosomal dominant, but the penetrance is incomplete and fewer than 50% of the offspring of affected parents are affected. Occasional patients with erythropoietic protoporphyria develop severe liver disease as a result of the accumulation of large amounts of protoporphyrin within hepatocytes: this form of the porphyria tends to be transmitted as an autosomal recessive trait, suggesting that homozygotes or compound heterozygotes (patients inheriting two mutations on different alleles) are at risk of the liver disease (See Inheritance of porphyria).

Clinical Effects
Hands of a patient with EPPPatients develop skin disease only and are not at risk of the acute attack. The skin disease associated with erythropoietic protoporphyria is characteristic, and does not conform to the same pattern of vesiculo-erosive photodermatitis seen in other forms of porphyria (See Skin disease in porphyria). Accumulation of porphyrins in the erythrocytes, plasma and skin leads to an unusual syndrome of immediate photosensitivity, felt by the patient as warmth, burning, stinging and pain in sun-exposed areas. This is sometimes described as solar urticaria. Typically patients have an individual threshold for sun-exposure. They learn that once they have been exposed to sun for more than a certain period of time (usually about 30 minutes) the symptoms will start. Immediately after sun exposure, the skin may be erythematous and oedematous. Patients do not develop the erosions and blisters typical of other forms of porphyria. Eventually chronic changes develop: these are limited to mild coarsening and grooving of the skin over the bridge of the nose and the knuckles (Click on the image).

Occasional patients with erythropoietic protoporphyria develop liver disease, known as protoporphyric hepatopathy. This results from the accumulation of large amounts of protoporphyrin in hepatocytes, which leads to disturbed liver function, cirrhosis and ultimately liver failure. Such patients are candidates for liver transplantation.

Source: Courtesy of Porphyria SA - UCT