Study summary · research use only
Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses the erythropoietic protoporphyrias, three rare genetic disorders (EPP1, XLEPP, and EPP2) that cause protoporphyrin IX (PPIX) buildup in erythrocytes and childhood-onset phototoxic skin pain. Diagnosis is confirmed by erythrocyte metal-free PPIX ≥3 times the upper limit of normal. It describes complications including liver failure, gallstones, anaemia, and vitamin D deficiency with reduced bone mineral density, and management approaches including vitamin D supplementation and DEXA scans. The review notes iron supplementation may increase photosensitivity in EPP1 but can reduce PPIX levels and liver damage in XLEPP, and lists phlebotomies, exchange transfusions, and liver transplantation with stem cell transplantation as options. Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is described as the only approved treatment reported to increase pain-free sunlight exposure and quality of life.
Abstract
The erythropoietic protoporphyrias consist of three ultra-rare genetic disorders of the erythroid heme biosynthesis, including erythropoietic protoporphyria (EPP1), X-linked protoporphyria (XLEPP) and CLPX-protoporphyria (EPP2), which all lead to the accumulation of protoporphyrin IX (PPIX) in erythrocytes. Affected patients usually present from early childhood with episodes of severe phototoxic pain in the skin exposed to visible light. The quantification of PPIX in erythrocytes with a metal-free PPIX ≥3 times the upper limit of normal confirms the diagnosis. Protoporphyria-related complications include liver failure, gallstones, mild anaemia and vitamin D deficiency with reduced bone mineral density. The management is focused on preventing phototoxic reactions and treating the complications. Vitamin D should be supplemented, and DEXA scans in adults should be considered. In EPP1, even in cases of biochemically determined iron deficiency, supplementation of iron may stimulate PPIX production, resulting in an increase in photosensitivity and the risk of cholestatic liver disease. However, for patients with XLEPP, iron supplementation can reduce PPIX levels, phototoxicity and liver damage. Because of its rarity, there is little data on the management of EPP-related liver disease. As a first measure, any hepatotoxins should be eliminated. Depending on the severity of the liver disease, phlebotomies, exchange transfusions and ultimately liver transplantation with subsequent haematopoietic stem cell transplantation (HSCT) are therapeutic options, whereby multidisciplinary management including porphyria experts is mandatory. Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life.
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