Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management.

Autor: Minder AE; Division of Endocrinology, Diabetology, and Porphyria, Stadtspital Zürich Triemli, Zurich, Switzerland.; Swiss Reference Centre for Porphyrias, Stadtspital Zürich Triemli, Zurich, Switzerland., Kluijver LG; Department of Internal Medicine, Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Barman-Aksözen J; Swiss Reference Centre for Porphyrias, Stadtspital Zürich Triemli, Zurich, Switzerland.; Institute of Laboratory Medicine, Stadtspital Zürich Triemli, Zurich, Switzerland.; University of Zurich, Zurich, Switzerland., Minder EI; Division of Endocrinology, Diabetology, and Porphyria, Stadtspital Zürich Triemli, Zurich, Switzerland.; Swiss Reference Centre for Porphyrias, Stadtspital Zürich Triemli, Zurich, Switzerland.; University of Zurich, Zurich, Switzerland., Langendonk JG; Department of Internal Medicine, Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2025 Jan; Vol. 45 (1), pp. e16027. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1111/liv.16027
Abstrakt: 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.
(© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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