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    831 results match your criteria Congenital Erythropoietic Porphyria

    1 OF 17

    Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity.
    J Inherit Metab Dis 2017 Feb 9. Epub 2017 Feb 9.
    Porphyria Centre San Gallicano Dermatological Institute IRCCS, Rome, Italy.
    Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. Read More

    Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.
    Haematologica 2017 Feb 10;102(2):260-270. Epub 2016 Nov 10.
    INSERM U1149/ERL CNRS 8252, Centre de Recherche sur l'Inflammation Paris Montmartre, 75018 Paris, France
    Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Read More

    Acute hepatic and erythropoietic porphyrias: from ALA synthases 1 and 2 to new molecular bases and treatments.
    Curr Opin Hematol 2017 Jan 21. Epub 2017 Jan 21.
    aINSERM U1149 CNRS ERL 8252, Centre de Recherche sur l'inflammation, Université Paris Diderot, site Bichat, Sorbonne Paris Cité bLaboratory of excellence, GR-Ex, Paris cAP-HP, Centre Français des Porphyries, Hôpital Louis Mourier, Colombes dAP-HP, Hôpital Beaujon, Service de Biochimie Clinique, Clichy, France.
    Purpose Of Review: Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies. Read More

    Modelling the ferrochelatase c.315-48C modifier mutation for erythropoietic protoporphyria (EPP) in mice.
    Dis Model Mech 2017 Jan 12. Epub 2017 Jan 12.
    Institute of Laboratory Medicine, Municipal Hospital Triemli, 8063 Zürich, Switzerland
    Erythropoietic Protoporphyria (EPP) is caused by deficiency of ferrochelatase (FECH) which incorporates iron into protoporphyrin IX (PPIX) to form heme. Excitation of accumulated PPIX by light generates oxygen radicals which evoke excessive pain and, after longer light exposure, ulcerations in exposed skin areas of EPP patients. Moreover, ∼5% of the patients develop a liver dysfunction due to PPIX accumulation. Read More

    Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders.
    Clin Pharmacokinet 2017 Jan 6. Epub 2017 Jan 6.
    Stadtspital Triemli, Institute of Laboratory Medicine, Zurich, Switzerland.
    Afamelanotide, the first α-melanocyte-stimulating hormone (MSH) analogue, synthesized in 1980, was broadly investigated in all aspects of pigmentation because its activity and stability were higher than the natural hormone. Afamelanotide binds to the melanocortin-1 receptor (MC1R), and MC1R signaling increases melanin synthesis, induces antioxidant activities, enhances DNA repair processes and modulates inflammation. The loss-of-function variants of the MC1R present in fair-skinned Caucasians are less effectively activated by the natural hormone. Read More

    Advances in the management of erythropoietic protoporphyria - role of afamelanotide.
    Appl Clin Genet 2016 12;9:179-189. Epub 2016 Dec 12.
    Department of Internal Medicine, Section on Gastroenterology.
    Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. Read More

    Case Report of Patient With Erythropoietic Protoporphyria and Basal Cell Carcinoma Diagnoses.
    J Cutan Med Surg 2016 Nov 11. Epub 2016 Nov 11.
    Department of Internal Medicine, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
    Background: Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. There is a clear association between BCC development and ultraviolet (UV) radiation. Erythropoietic protoporphyria (EPP) is an inherited porphyria disorder that is a result of protoporphyrin accumulation, typically manifesting with phototoxicity. Read More

    Hepatic porphyria: A narrative review.
    Indian J Gastroenterol 2016 Nov 31;35(6):405-418. Epub 2016 Oct 31.
    Department of Internal Medicine, UAB University of Alabama in Birmingham, Birmingham, AL, USA.
    Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). Read More

    Clinical, Biochemical and Molecular Characteristics of the Main Types of Porphyria.
    Adv Clin Exp Med 2016 Mar-Apr;25(2):361-8
    Department of Haemostasis and Metabolic Disorders of the Institute of Haematology and Transfusion Medicine, Warszawa, Poland.
    Porphyrias are diverse disorders that arise from various inherited enzyme defects in the heme biosynthesis pathway, except for porphyria cutanea tarda (PCT), in which the enzyme deficiency in most cases is acquired. The biosynthetic blocks resulting from the defective enzymes are largely expressed either in the liver or bone marrow, the sites where the majority of heme is produced. Although the pathophysiologic mechanisms of the clinical manifestations of the porphyrias are not fully understood, two cardinal features prevail: skin photosensitivity and neurologic symptoms of intermittent autonomic neuropathy, acute neurovisceral attacks, and disorders of the nervous system. Read More

    Congenital Erythropoietic Porphyria with Undescended Testis.
    Indian J Dermatol 2016 Jul-Aug;61(4):467
    Department of Dermatology, Army College of Medical Sciences, New Delhi, India.
    Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis pathway that are characterized by acute neurovisceral symptoms, skin lesions, or both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with a mutation in the gene that codes for uroporphyrinogen III synthase leading to accumulation of porphyrin in different tissues and marked cutaneous photosensitivity. We report a case of CEP with infancy onset blistering, photosensitivity, red colored urine, and teeth along with scarring. Read More

    Novel Treatment Using Cimetidine for Erythropoietic Protoporphyria in Children.
    JAMA Dermatol 2016 Nov;152(11):1258-1261
    Department of Dermatology, Stanford University, Stanford, California.
    Importance: Erythropoietic protoporphyria (EPP) is a rare hereditary disease of heme biosynthesis that manifests as severe photosensitivity and hepatotoxicity. There have been no effective treatments to date. Cimetidine has been shown to inhibit heme biosynthesis and results in symptomatic improvement in patients with acute intermittent porphyria (AIP) and porphyria cutanea tarda (PCT). Read More

    A case of erythropoietic protoporphyria.
    Proc (Bayl Univ Med Cent) 2016 Jul;29(3):311-2
    Department of Pathology, University of South Carolina, Charleston (Lindsey); and the Departments of Hematology/Oncology (Burch) and Pathology (Krause), Baylor University Medical Center at Dallas and Baylor Sammons Cancer Center, Dallas, Texas.
    A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Read More

    Cutaneous Porphyrias: Causes, Symptoms, Treatments and the Danish Incidence 1989-2013.
    Acta Derm Venereol 2016 Nov;96(7):868-872
    Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense C, Denmark.
    Porphyrias are rare diseases caused by altered haem synthesis leading to the accumulation of different haem intermediates. Neurovisceral attacks may occur in acute porphyrias, while photosensitivity is the presenting symptom in cutaneous porphyrias. We present here an overview of symptoms and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. Read More

    Late-onset cutaneous porphyria in a patient heterozygous for a uroporphyrinogen III synthase gene mutation.
    Br J Dermatol 2016 Dec 11;175(6):1346-1350. Epub 2016 Aug 11.
    Departments of Dermatology, Biochemistry and Molecular Genetics, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
    Deficiency of uroporphyrinogen III synthase (UROS) causes congenital erythropoietic porphyria (CEP). The disease, originating from the inheritance of mutations within the UROS gene, presents a recessive form of transmission. In a few patients, a late-onset CEP-like phenotype without UROS mutations appears to be associated with a myelodysplastic syndrome. Read More

    Advances in understanding the pathogenesis of congenital erythropoietic porphyria.
    Br J Haematol 2016 May 11;173(3):365-79. Epub 2016 Mar 11.
    U.O. di Medicina Interna, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milano, Italy.
    Congenital erythropoietic porphyria (CEP) is a rare genetic disease resulting from the remarkable deficient activity of uroporphyrinogen III synthase, the fourth enzyme of the haem biosynthetic pathway. This enzyme defect results in overproduction of the non-physiological and pathogenic porphyrin isomers, uroporphyrin I and coproporphyrin I. The predominant clinical characteristics of CEP include bullous cutaneous photosensitivity to visible light from early infancy, progressive photomutilation and chronic haemolytic anaemia. Read More

    A Rare Case of Puberty Onset Congenital Erythropoietic Porphyria with Ophthalmological Manifestations.
    Middle East Afr J Ophthalmol 2016 Jan-Mar;23(1):160-2
    Department of Ophthalmology, Nil Ratan Sircar (NRS) Medical College and Hospital, Kolkata, West Bengal, India.
    A 27-year-old male patient was presented with foreign body sensation in both the eyes for 2 years duration and blisters followed by scarring and pigmentation in the photo-exposed areas of the body over the previous 12 years. His urine was reddish colored for the previous year. On examination, there was scarring, hyper-pigmentation of photo-exposed parts of the body along with resorption of the distal phalanges of fingers in both hands except the smallest digit which had onycholysis. Read More

    The emerging role of GATA transcription factors in development and disease.
    Expert Rev Mol Med 2016 Mar 8;18:e3. Epub 2016 Mar 8.
    Department of Pathology,GROW - School for Oncology and Developmental Biology,Maastricht University Medical Center,Maastricht,The Netherlands.
    The GATA family of transcription factors consists of six proteins (GATA1-6) which are involved in a variety of physiological and pathological processes. GATA1/2/3 are required for differentiation of mesoderm and ectoderm-derived tissues, including the haematopoietic and central nervous system. GATA4/5/6 are implicated in development and differentiation of endoderm- and mesoderm-derived tissues such as induction of differentiation of embryonic stem cells, cardiovascular embryogenesis and guidance of epithelial cell differentiation in the adult. Read More

    Scleral necrosis in congenital erythropoietic porphyria: A case report and review of the literature.
    Oman J Ophthalmol 2015 Sep-Dec;8(3):200-4
    Department of Cornea and Ocular Surface Disorders, Sankara Nethralaya, Chennai, Tamil Nadu, India.
    A 28-year-old presented with complaints of severe pain and redness in the left eye since 2 weeks. He had similar complaints in the right eye 2 years back for which he had undergone a scleral patch graft. Best corrected visual acuity was 20/20 in both eyes. Read More

    A Novel Mutation in the FECH Gene in a Czech Family with Erythropoietic Protoporphyria and a Population Study of IVS3-48C Variant Contributing to the Disease.
    Folia Biol (Praha) 2015 ;61(6):227-32
    Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
    Erythropoietic protoporphyria (EPP), a chronic erythropoietic porphyria, is characterized by excess accumulation of protoporphyrin, particularly in erythroid cells. EPP inheritance is complex, almost always associated with two molecular defects. In most EPP patients, clinical expression requires coinheritance of a private ferrochelatase (FECH) mutation trans- to a hypomorphic FECH*IVS3-48C allele. Read More

    [Erythropoietic protoporphyria : Clinical manifestations, diagnosis and new therapeutic possibilities].
    Hautarzt 2016 Mar;67(3):211-5
    Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Moorenstr. 5, Deutschland.
    Background: Erythropoietic protoporphyria, the second most common type of the cutaneous porphyrias, is due to an enzymatic deficiency of ferrochelatase, the last enzyme in heme biosynthesis. The enzyme defect leads to an accumulation of protoporphyrin IX in erythrocytes and an elevated excretion of this metabolite in the feces.

    Clinical Presentation: Usually, disease onset is in early infancy, characterized by increased photosensitivity. Read More

    [Congenital erythropoietic porphyria : An update].
    Hautarzt 2016 Mar;67(3):216-20
    Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich Heine Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.
    Background: Congenital erythropoetic porphria is a very rare type of autosomal recessive nonacute porphyria. Homozygous or compound heterozygous mutations in the uroporphyrinogen III consynthase gene cause a marked enzymatic deficiency of uroporphyrinogen III consynthase, the fourth enzyme along the heme biosynthetic pathway.

    Clinical Presentation: Clinically, affected patients are characterized by a moderate to severe photosensitivity. Read More

    Biology of Heme in Mammalian Erythroid Cells and Related Disorders.
    Biomed Res Int 2015 18;2015:278536. Epub 2015 Oct 18.
    Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan ; Molecular Hematology/Oncology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
    Heme is a prosthetic group comprising ferrous iron (Fe(2+)) and protoporphyrin IX and is an essential cofactor in various biological processes such as oxygen transport (hemoglobin) and storage (myoglobin) and electron transfer (respiratory cytochromes) in addition to its role as a structural component of hemoproteins. Heme biosynthesis is induced during erythroid differentiation and is coordinated with the expression of genes involved in globin formation and iron acquisition/transport. However, erythroid and nonerythroid cells exhibit distinct differences in the heme biosynthetic pathway regulation. Read More

    Congenital Erythropoietic Porphyria With Calcific Constrictive Pericarditis: A Case Report and Brief Review of Literature.
    World J Pediatr Congenit Heart Surg 2015 Oct;6(4):646-9
    Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi, India.
    An 18-year-old boy with congenital erythropoietic porphyria and calcific constrictive pericarditis underwent total pericardiectomy. The cause of pericardial calcification could be deposition of porphyrins in the pericardium. Surgical importance of this rare condition is highlighted. Read More

    A metabolomic perspective of griseofulvin-induced liver injury in mice.
    Biochem Pharmacol 2015 Dec 5;98(3):493-501. Epub 2015 Sep 5.
    Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address:
    Griseofulvin (GSF) causes hepatic porphyria in mice, which mimics the liver injury associated with erythropoietic protoporphyria (EPP) in humans. The current study investigated the biochemical basis of GSF-induced liver injury in mice using a metabolimic approach. GSF treatment in mice resulted in significant accumulations of protoporphyrin IX (PPIX), N-methyl PPIX, bile acids, and glutathione (GSH) in the liver. Read More

    ClinLabGeneticist: a tool for clinical management of genetic variants from whole exome sequencing in clinical genetic laboratories.
    Genome Med 2015 Jul 29;7:77. Epub 2015 Jul 29.
    Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Routine clinical application of whole exome sequencing remains challenging due to difficulties in variant interpretation, large dataset management, and workflow integration. We describe a tool named ClinLabGeneticist to implement a workflow in clinical laboratories for management of variant assessment in genetic testing and disease diagnosis. We established an extensive variant annotation data source for the identification of pathogenic variants. Read More

    Incomplete erythropoietic protoporphyria caused by a splice site modulator homozygous IVS3-48C polymorphism in the ferrochelatase gene.
    Br J Dermatol 2016 Jan 7;174(1):172-5. Epub 2015 Nov 7.
    Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, 930-0194, Japan.
    Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by both the partial deficiency of ferrochelatase (FECH) and the existence of cytosine at IVS3-48 in trans to a mutated FECH allele. However, physicians occasionally encounter patients with EPP with a mild phenotype associated with a slight increase in the erythrocyte-free protoporphyrin concentration and no FECH gene mutations. In this study, genetic analyses were performed on three patients with a mild phenotype of EPP, with photosensitivity, slightly increased erythrocyte-free protoporphyrin concentrations and only a few fluorocytes in the peripheral blood. Read More

    Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and Exogenous Porphyrinogenic Stress.
    J Biol Chem 2015 Sep 23;290(39):23711-24. Epub 2015 Jul 23.
    From the Departments of Molecular and Integrative Physiology, Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109 and the Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan 48105.
    Hepatic accumulation of protoporphyrin-IX (PP-IX) in erythropoietic protoporphyria (EPP) or X-linked-dominant protoporphyria (XLP) cause liver damage. Hepatocyte nuclear lamin aggregation is a sensitive marker for PP-IX-mediated liver injury. We tested the hypothesis that extracellular or intracellular protoporphyria cause damage to different subcellular compartments, in a light-triggered manner. Read More

    Porphyrias: A 2015 update.
    Clin Res Hepatol Gastroenterol 2015 Sep 2;39(4):412-25. Epub 2015 Jul 2.
    INSERM U1149 CNRS ERL 8252, centre de recherche sur l'inflammation, 16, rue Henri-Huchard, 75018 Paris, France; Université Versailles-Saint-Quentin, 55, Avenue de Paris, 78000 Versailles, France; Université Paris Diderot, site Bichat, Sorbonne Paris Cité, 75018 Paris, France; Centre français des porphyries, hôpital Louis-Mourier, AP-HP, 92701 Colombes, France. Electronic address:
    The hereditary porphyrias comprise a group of eight metabolic disorders of the heme biosynthesis pathway. Each porphyria is caused by abnormal function at a separate enzymatic step resulting in a specific accumulation of heme precursors. Porphyrias are classified as hepatic or erythropoietic, based on the organ system in which heme precursors (δ-aminolevulinic acid [ALA], porphobilinogen and porphyrins) are overproduced. Read More

    Bovine congenital erythropoietic protoporphyria in a crossbred limousin heifer in Ireland.
    Ir Vet J 2015 2;68(1):15. Epub 2015 Jul 2.
    School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
    An unusual case of an 11-month-old, black Limousin-cross heifer, with an 8-month history of episodic seizures and photosensitisation, was referred by a veterinary practitioner to the Farm Animal Section of the UCD Veterinary Hospital, School of Veterinary Medicine, University College Dublin, Ireland, in August 2014. Following an investigation, a diagnosis of Bovine Congenital Erythropoietic Protoporphyria (BCEPP) was made. To the authors' knowledge this is the first report of such a case in Ireland. Read More

    Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias.
    Curr Protoc Hum Genet 2015 Jul 1;86:17.20.1-26. Epub 2015 Jul 1.
    Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas.
    Porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), δ-aminolevulinic acid dehydratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP). Read More

    Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria.
    Blood 2015 Jul 13;126(2):257-61. Epub 2015 May 13.
    Department of Medicine, Division of Hematology, University of Washington, Seattle, WA; and.
    Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme synthesis characterized by reduced activity of uroporphyrinogen III synthase and the accumulation of nonphysiologic isomer I porphyrin metabolites, resulting in ineffective erythropoiesis and devastating skin photosensitivity. Management of the disease primarily consists of supportive measures. Increased activity of 5-aminolevulinate synthase 2 (ALAS2) has been shown to adversely modify the disease phenotype. Read More

    Bone marrow transplant for X-linked protoporphyria with severe hepatic fibrosis.
    Pediatr Transplant 2015 Jun 9;19(4):E106-10. Epub 2015 Apr 9.
    Department of Pediatrics, Childrens Mercy Hospital, Kansas City, MO, USA.
    XLP is an erythroid porphyria that results in variable cutaneous photosensitivity due to accumulation of protoporphyrin. The genetic defect in XLP is mutation of the gene ALAS2, resulting in gain of function for the erythroid enzyme 5-aminolevulinate synthase 2. Previous reports have shown that protoporphyrin-induced liver disease may also occur in XLP, occasionally severe enough to warrant liver transplantation; however, transplantation may be followed by injury to the graft due to continued presence of the underlying metabolic disorder in the bone marrow. Read More

    [Update on the biology of heme synthesis in erythroid cells].
    Rinsho Ketsueki 2015 Feb;56(2):119-27
    Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine.
    Heme is a prosthetic group of hemoproteins playing important roles in oxygen transport, detoxification, circadian rhythm, microRNA processing, regulation of transcription, and translation. The majority of heme (-85%) is synthesized in red blood cells mainly for hemoglobin production, whereas hepatocytes account for most of the rest, functioning primarily in the synthesis of cytochrome P450 enzymes and mitochondrial respiratory enzymes. Thus, failure of heme biosynthesis causes severe inherited or acquired disorders in humans, including porphyria and sideroblastic anemia. Read More

    X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria.
    Clin Genet 2016 Jan 17;89(1):20-6. Epub 2015 Feb 17.
    Fondazione IRCCS "Cà-Granda" Ospedale Maggiore Policlinico, U.O. di Medicina Interna, Milano, Italy.
    X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. Read More

    Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria.
    Br J Dermatol 2015 Jun 30;172(6):1601-12. Epub 2015 Apr 30.
    Institute of Laboratory Medicine, Municipal Hospital Triemli, Zurich, Switzerland.
    Background: In erythropoietic protoporphyria (EPP), an inherited disease of porphyrin-biosynthesis, the accumulation of protoporphyrin in the skin causes severely painful phototoxic reactions. Symptom prevention was impossible until recently when afamelanotide became available. Afamelanotide-induced skin pigmentation has statistically significantly improved light-tolerance, although the clinical significance of the statistical effect was unknown. Read More

    Evaluation of the immunogenicity of the synthetic α-melanocyte-stimulating hormone (α-MSH) analogue afamelanotide ([Nle4-D-Phe7]-α-MSH, Scenesse®) in erythropoietic protoporphyria patients by ELISA detecting both anti-afamelanotide and anti-α-MSH antibodies.
    Skin Pharmacol Physiol 2015 13;28(2):103-13. Epub 2014 Nov 13.
    Unilabs Dr. Weber, St. Gallen, Switzerland.
    Unlabelled: Afamelanotide is an α-melanocyte-stimulating hormone (α-MSH) agonist with proven efficacy in photodermatoses such as erythropoietic protoporphyria (EPP). This peptide drug, repeatedly administered over prolonged time, may induce anti-drug antibodies (ADA). Here, we describe a new ELISA method developed to monitor the occurrence of ADA against afamelanotide as well as against α-MSH. Read More

    Clinically important features of porphyrin and heme metabolism and the porphyrias.
    Metabolites 2014 Nov 3;4(4):977-1006. Epub 2014 Nov 3.
    Department of Medicine, Universities of CT, Farmington, CT 06030 and North Carolina, Chapel Hill, NC 27599, USA.
    Heme, like chlorophyll, is a primordial molecule and is one of the fundamental pigments of life. Disorders of normal heme synthesis may cause human diseases, including certain anemias (X-linked sideroblastic anemias) and porphyrias. Porphyrias are classified as hepatic and erythropoietic porphyrias based on the organ system in which heme precursors (5-aminolevulinic acid (ALA), porphobilinogen and porphyrins) are chiefly overproduced. Read More

    Congenital erythropoietic porphyria linked to GATA1-R216W mutation: challenges for diagnosis.
    Eur J Haematol 2015 Jun 25;94(6):491-7. Epub 2014 Oct 25.
    Fondazione IRCCS "Cà-Granda" Ospedale Maggiore Policlinico, U.O. di Medicina Interna, Milan, Italy.
    Congenital erythropoietic porphyria (CEP) is a rare genetic disease that is characterized by a severe cutaneous photosensitivity causing unrecoverable deformities, chronic hemolytic anemia requiring blood transfusion program, and by fatal systemic complications. A correct and early diagnosis is required to develop a management plan that is appropriate to the patient's needs. Recently only one case of X-linked CEP had been reported, describing the trans-acting GATA1-R216W mutation. Read More

    In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability.
    Blood Cells Mol Dis 2015 Jan 30;54(1):71-7. Epub 2014 Aug 30.
    Institute of Laboratory Medicine, Triemli Hospital, Zürich, Switzerland. Electronic address:
    The activity of the erythroid-specific isoenzyme of 5-aminolevulinic acid synthase (ALAS2), the first and rate-limiting enzyme in heme biosynthesis, is down-regulated during iron-deficiency. Ferrochelatase (FECH), the last enzyme of this pathway, inserts iron into protoporphyrin IX (PPIX) to form heme. Patients with erythropoietic protoporphyria (EPP), an inherited deficiency in FECH, often show signs of iron deficiency in addition to phototoxicity which is caused by PPIX accumulation. Read More

    Identification of mutations in the uroporphyrinogen III synthase gene in a Thai girl patient with congenital erythropoietic porphyria.
    Int J Lab Hematol 2015 Apr 5;37(2):e44-7. Epub 2014 Aug 5.
    Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

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