1,016 results match your criteria: "Congenital Erythropoietic Porphyria"

Inhibition of ABCG2 prevents phototoxicity in a mouse model of erythropoietic protoporphyria.

Nat Commun

December 2024

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.

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Erythropoietic protoporphyria (EPP1) results in painful photosensitivity and severe liver damage in humans due to the accumulation of fluorescent protoporphyrin IX (PPIX). While zebrafish () models for porphyria exist, the utility of ferrochelatase () knockout zebrafish, which exhibit EPP, for therapeutic screening and biological studies remains unexplored. This study investigated the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated -knockout zebrafish larvae as a model of EPP1 for drug screening.

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The impact of minimal sunlight exposure on bone health: insights from a cohort study in erythropoietic protoporphyria.

J Clin Endocrinol Metab

October 2024

Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, the Netherland.

Article Synopsis
  • Erythropoietic protoporphyria (EPP) is an inherited metabolic disease that leads to painful reactions to sunlight and increased risk of osteoporosis due to low bone mineral density (BMD) and vitamin D deficiency.
  • A study on EPP patients revealed that a significant majority had low BMD, with 39.5% classified as osteopenic and 15.3% as osteoporotic, alongside a high incidence of related fractures.
  • The findings highlight the importance of maintaining adequate vitamin D levels for improving BMD, while treatments like afamelanotide did not show effectiveness.
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  • A 28-year-old man with erythropoietic porphyria experienced a severe worsening of symptoms after receiving an intravenous iron infusion, leading to a painful rash, nausea, and abnormal lab results.
  • Multidisciplinary care from dermatology, gastrointestinal, and hematology specialists was crucial for his recovery, which included strict light avoidance and other symptom management strategies.
  • The case highlights the need for awareness of triggers, timely diagnosis, ongoing follow-up, and the potential importance of genetic counseling in managing EPP.
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  • A young anemic woman developed liver failure and swelling after taking ferrous sulfate, leading to the discovery of her congenital erythropoietic porphyria (CEP) through a skin exam and lab tests.
  • She received treatment that included IV methylprednisolone, blood transfusions, vitamins, and wound care.
  • The report highlights the need for doctors to be aware of CEP, as it can be mistaken for other conditions and reactions due to its rarity.
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  • - Protoporphyria, a type of porphyria, causes extreme skin reactions to certain light wavelengths, but patients typically avoid sunlight rather than phototherapy.
  • - A case report details a neonate who, unbeknownst to have X-linked protoporphyria, experienced severe complications after brief phototherapy, including a rash, acute liver failure, and respiratory issues.
  • - This situation highlights the need for healthcare providers to promptly recognize and address unusual reactions to phototherapy in neonates, considering protoporphyria as a possible cause.
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Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management.

Liver Int

July 2024

Department of Internal Medicine, Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Disease, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Article Synopsis
  • The erythropoietic protoporphyrias are three rare genetic disorders that disrupt heme production, causing a buildup of protoporphyrin IX (PPIX) in red blood cells and leading to severe skin pain from light exposure, starting in early childhood.
  • Diagnosis involves measuring PPIX levels in the blood, and complications can include liver issues, gallstones, anemia, and vitamin D deficiency.
  • Management focuses on avoiding light triggers, addressing complications, and using treatments like afamelanotide to improve quality of life, with careful consideration of iron supplementation depending on the specific disorder.
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  • Heme biosynthesis is crucial for functions like oxygen transport, but it must be carefully regulated to avoid toxic buildup and iron depletion.
  • The enzyme ALA synthase (ALAS) is degraded when excess heme is present, and this process involves the protein POLDIP2, which helps target ALAS for degradation by the CLPXP protease complex.
  • Research reveals that POLDIP2 specifically recognizes heme-bound ALAS, facilitating its removal from the cell, and identifies the mechanisms involved in this regulation, which are linked to certain forms of porphyria.
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  • Erythropoietic protoporphyria (EPP) is a genetic disorder caused by mutations in the ferrochelatase gene, leading to a harmful build-up of protoporphyrin IX mainly affecting blood cells, skin, and the liver.
  • A case study of a 35-year-old male with liver issues due to EPP showed that combining red blood cell exchange and therapeutic plasma exchange significantly improved his symptoms and lowered bilirubin levels.
  • The results indicate that this combined treatment approach may be a promising option for managing severe liver impairment in patients with EPP.
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  • Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare conditions causing severe skin reactions to sunlight, and afamelanotide is the only approved treatment that enhances light tolerance and quality of life (QoL).
  • A study conducted at Massachusetts General Hospital evaluated 29 adults who received afamelanotide, showing that patients experienced significant increases in time before phototoxic symptoms appeared after sunlight exposure, indicating improved light tolerance.
  • Despite these benefits in light tolerance and QoL, the treatment did not result in improvements in laboratory markers of protoporphyria or liver function.
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Quality of life in children with erythropoietic protoporphyria: a case-control study.

J Dermatol

August 2024

Department of Internal Medicine, Porphyria Center Rotterdam, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Article Synopsis
  • Erythropoietic protoporphyria (EPP) is a genetic disorder that leads to painful reactions to sunlight, significantly affecting the quality of life (QoL) of both children and adults.
  • This study compared QoL scores between children with EPP and matched healthy controls, revealing lower scores in physical and social aspects for the EPP group, though not statistically significant after adjustment.
  • While children's overall EPP-QoL scores were similar to those of adults with EPP, they showed significantly lower scores in the disease-specific subdomain, highlighting the urgent need for treatment options and further research for affected children.
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[An overview of porphyrias].

Dermatologie (Heidelb)

July 2024

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen, Robert Koch Str. 40, 37075, Göttingen, Deutschland.

Article Synopsis
  • Porphyrias are genetic metabolic disorders that disrupt enzymes involved in producing porphyrin and heme, leading to toxic byproducts like porphyrins.
  • Symptoms vary widely, including skin issues in sunlight and dangerous neurovisceral attacks.
  • Diagnosis involves biochemical tests of urine, blood, and stool, and treatment is complex, often needing collaboration among various medical specialists.
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  • X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are rare genetic diseases caused by mutations affecting the enzyme ALAS2, crucial for heme production, with XLSA resulting from loss-of-function and XLPP from gain-of-function mutations.
  • Researchers created knockin mouse models using CRISPR-CAS9 to study these diseases along with a model for congenital sideroblastic anemia (CSA) linked to SLC25A38 mutations, allowing for in-depth examination of disease characteristics and responses to dietary vitamin B6.
  • The study revealed varying sensitivities to pyridoxine deficiency across models, highlighting a unique lethal interaction between certain sideroblastic anemias and vitamin
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Exploring current and emerging therapies for porphyrias.

Liver Int

September 2024

Solid Tumors Program, Hepatology: Porphyrias & Carcinogenesis Laboratory, CIMA-University of Navarra, Pamplona, Spain.

Article Synopsis
  • Porphyrias are rare inherited disorders caused by enzyme activity changes in haem synthesis, leading to the buildup of harmful intermediates that cause skin and nerve issues due to their photoreactive and neurotoxic properties.
  • Current treatments are not very effective, and there's limited understanding of how they work, prompting research into new therapies that target the root causes of the disease through gene therapy and molecular techniques.
  • Advances in nanotechnology are improving drug delivery systems, allowing for better treatment options and the potential for repurposing existing medications to help manage porphyrias effectively.
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Article Synopsis
  • - NICE uses quality-adjusted life years (QALYs) to evaluate the cost-effectiveness of treatments, combining clinical benefits with the duration of patient benefits.
  • - A study on NICE's evaluations for rare diseases found that the median time horizon for QALY calculations was 97.5 years, often exceeding expected treatment durations or life expectancies.
  • - The only treatment with a negative funding decision had a shorter time horizon than the expected treatment duration, raising concerns about the fairness and consistency of NICE's evaluation process.
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  • Afamelanotide is a synthetic hormone that increases the production of eumelanin, providing stronger effects than natural hormones.
  • It has been used since 2016 to treat erythropoietic porphyria (EPP), a condition causing painful sensitivity to light.
  • The hormone has shown positive outcomes such as better tolerance to artificial light and reduced pain when exposed to sunlight, suggesting it should be considered in dermatological treatments.
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  • - The text summarizes the historical progression of understanding porphyrias, a group of disorders linked to haem biosynthesis, starting from the first cases reported in the 19th century to significant contributions by scientists like Meyer-Betz, Günther, and Waldenström.
  • - Major breakthroughs include the classification and identification of different types of porphyrias, the discovery of porphobilinogen’s role in acute porphyria, and Hans Fischer's Nobel-winning work on porphyrin structure and haemin synthesis in the early 20th century.
  • - By 2000, advancements in genetic research allowed for the cloning and sequencing of haem biosynthesis genes, leading to improved understanding of inherited porphyrias and the development of
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  • Congenital erythropoietic porphyria (CEP) is a rare genetic disorder caused by reduced function of the UROS enzyme, leading to the accumulation of harmful porphyrins.
  • The buildup of these porphyrins mainly affects blood and skin, causing symptoms that can range from severe fetal conditions to mild skin issues in adults.
  • The text discusses the biochemical and clinical aspects of CEP, alongside current and potential new treatments aimed at improving UROS enzyme activity.
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Article Synopsis
  • Porphyria is a genetic disorder affecting heme biosynthesis, leading to a buildup of porphyrins in organs, especially the liver, which can result in severe conditions like cholestasis and liver cirrhosis.* -
  • Congenital erythropoietic porphyria (CEP) is a rare type of porphyria caused by a specific enzyme deficiency, primarily causing skin issues but also potentially affecting the liver with fibrosis.* -
  • A unique case is reported of a CEP patient who developed porto-sinusoidal vascular disease, leading to complications like portal hypertension that required liver transplantation.*
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The effects of cholecalciferol and afamelanotide on vitamin D levels in erythropoietic protoporphyria: a multicentre cohort study.

Br J Dermatol

August 2024

Porphyria Centre Rotterdam, Centre for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Centre, Rotterdam, the Netherlands.

Article Synopsis
  • Patients with erythropoietic protoporphyria (EPP) often experience painful photosensitivity and have a high prevalence of vitamin D deficiency and osteoporosis, even after starting treatment with the drug afamelanotide, which has been available since 2016.
  • A study involving 230 EPP patients analyzed vitamin D levels from 2005 to 2021, comparing those who received different treatments, including afamelanotide and cholecalciferol (vitamin D3).
  • Results indicated that while afamelanotide alone did not significantly increase vitamin D levels, cholecalciferol and combined therapy with both treatments did lead to significant improvements, highlighting the importance of vitamin D supplementation for these patients.
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Article Synopsis
  • * The only known curative treatment for CEP is allogeneic stem cell transplantation (Allo-SCT), which has mainly been documented in children and not in adults.
  • * This study presents the first successful case of a 46-year-old man cured of CEP with Allo-SCT, showing promising results over a 5-year follow-up period.
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  • * Symptoms include severe skin reactions to sunlight, blistering, and other structural abnormalities, with some cases presenting during pregnancy.
  • * Management focuses on sun protection, beta-carotene treatment, and blood transfusions, with stem cell transplantation being the only potential cure; this case highlights the challenges in treating this complex disorder.
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