2026-03-12 | Hematopoietic stem cell transplantation for erythropoietic porphyria-induced acute liver failure: a case report and literature review.
Protoporphyrias are rare genetic disorders in heme biosynthesis, causing protoporphyrin IX accumulation with progressive liver injury. Liver transplantation has traditionally treated protoporphyria-induced liver injury but does not correct the underlying hematopoietic defect. We present a 16-year-old male with painful cutaneous photosensitivity who developed cholestatic liver dysfunction and severe abdominal pain. After plasmapheresis, red blood cell (RBC) transfusions, and intravenous hemin, he had transient improvement and subsequently underwent hematopoietic stem cell transplantation (HSCT) without liver transplantation, which normalized his protoporphyrin levels, liver function, and symptoms. This case underscores HSCT as a disease-modifying therapy that may prevent liver transplantation when performed before irreversible hepatic damage.
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2025-12-31 | Congenital Erythropoietic Porphyria with Persistent Severe Biochemical Abnormalities and a Non-Mutilating Clinical Course: A Case Report
Congenital erythropoietic porphyria (CEP), also known as Günther disease, is a rare autosomal recessive porphyria caused by deficiency of uroporphyrinogen III synthase, leading to accumulation of phototoxic type I porphyrins. CEP classically presents in infancy with severe photosensitivity, blistering, scarring, and hemolytic anemia; however, significant phenotypic variability has increasingly been recognized. We report 32-year-old women diagnosed with CEP in early infancy who demonstrated persistently and profoundly elevated erythrocyte porphyrin levels over more than a decade yet followed a relatively non-mutilating clinical course. Genetic testing identified a low penetrance intronic UROS variant typically associated with erythropoietic protoporphyria, underscoring diagnostic challenges and genotype-phenotype discordance. The patient experienced marked improvement in photosensitivity and burning pain after initiation of afamelanotide, without need for transfusion therapy or stem cell transplantation. This case highlights the heterogeneity of CEP, the importance of long-term biochemical follow up, and the potential role of afamelanotide in improving quality of life for selected patients with CEP.
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2025-12-30 | New pharmacotherapies for the erythropoietic protoporphyrias: an analysis of trial protocols from a patient perspective.
The erythropoietic protoporphyrias (EPP) are a group of ultra-rare (1:100.000) inborn errors of the heme biosynthesis characterised by painful phototoxic reactions in tissue exposed to visible light. Afamelanotide is the only approved treatment for EPP and effectively prevents phototoxic reactions and improves the quality of life of the patients. In the past years, several new potential treatment options for EPP have been identified, some of which are currently under investigation in clinical trials. While these developments could improve patient care, it is important to know how safety and efficacy of drug candidates compare to the existing treatment, i.e. afamelanotide. We identified pharmacotherapies (leaving out, for example, topical applications such as sunscreens or supplements such as iron) which are currently (that is, within the last 5 years) evaluated for EPP from clinical trial registries and investigated whether the trial designs allow a comparison of their treatment effects with each other and with afamelanotide. Therefore, we analysed the clinical trial protocols with emphasis on their trial designs, efficacy outcome measures, inclusion and exclusion criteria, safety aspects and, if available, published results. Our search in the clinical trials registries retrieved 29 trials that included patients with EPP. From these, we identified 16 clinical trials evaluating afamelanotide and three new pharmacotherapies, i.e., dersimelagon, bitopertin and cimetidine. Safety and efficacy of all new pharmacotherapies are currently being investigated against placebo-control groups or against baseline. Because of differences in the outcome measures and included patient populations, the results of the trials cannot be directly compared. Moreover, methodically challenging aspects and ethical issues were identified in some of the trial protocols. Efficacy and safety of currently investigated treatments for EPP are not directly comparable. We wrote this manuscript as a call to action to Principal Investigators, Ethical Review Boards, Regulatory Authorities and the sponsors of trials because we are convinced that trials directly assessing new pharmacotherapies against afamelanotide would be the more informative, and methodological and ethically sounder trial design. Not applicable. The online version contains supplementary material available at 10.1186/s13023-025-04170-9.
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