Erythropoietic protoporphyria

Rare inherited disorder of heme biosynthesis resulting from a partial deficiency of f2242ochelatase.

30-50% deficiency of f2242ochelatase activity.

Autosomal recessive inborn 2242or of metabolism.

There is an X-linked form accounting for 2-10% of cases and results from a gain
of function of erythroid specific aminolevulinic acid synthetase 2.

The disease occurs in all races and ethnic groups but it rare among blacks.

Massive excretion of protoporphyrin into stool.

Associated with mild to moderate photosensitivity and no hemolysis.

Associated with severe painful photosensitivity and results from accumulation of protoporphyrin in erythroid cells and tissues because of decreased activity of f2242ochelatase the heme biosynthetic that inserts iron in the protoporhyrin to form heme.

Photosensitivity usually manifests in early childhood and occurs 1-20 minutes after direct exposure to the sun. 

Patients may develop severe skin burns, typically on the hands and face.

Neuropathic pain can be incapacitating and last several days and does not respond to analgesics.

Onset in childhood with lifelong photosensitivity with overproduction and accumulation of protoporphyrin in erythropoietic cells, erythrocytes, skin, liver and plasma.

Generally a mild disease with some carriers having only mildly elevated protoporphyrin levels without skin photosensitivity.

Patients may develop porphyrin rich gallstones.

Rarely death may be associated with hepatic insufficiency.

Protoporphyrin is released from red cells into the circulation and gains access vascular endothelium and liver, and is excreted biliary tract.

Patients learn to avoid sunlight and have minimal light exposure, wear protective clothing or remain indoors.

When accumulated phototoxic protoporphyrin in the skin is exposed to sun or visible light (400-410 nm) itis activated by blue light triggering singlet oxygen free radicals reactions leading to neuropathic pain that may last for hours to days.

In about 5% of cases the protoporphyrin in transit to the liver may precipitate into gallstones and cause cholestatic hepatitis.

Cholestatic hepatitis may progress to liver failure and may be requirement for liver transplantation.

No effective therapy is available, although beta-carotene, and N-acetylene-L-cysteine and vitamin C have been used.

Afamelanotide (Scenesse) is an analog of human Alpha-melanocyte-stimulating hormone and binds to the melanocyte 1 receptor in dermal cells including melanocytes and increases the production of eumelanin in the epidermis without the ultra light violet light induced cellular damage that occurs when melanin production is stimulated light ultraviolet.

Afamelanotide (Scenesse) enables patience with this illness to have more direct exposure to sunlight without pain due to phototoxicity.

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