435 results match your criteria Variegate Porphyria

Update on the diagnosis and management of the autosomal dominant acute hepatic porphyrias.

J Clin Pathol 2022 May 18. Epub 2022 May 18.

Medical Biochemistry and Immunology, University Hospital of Wales Healthcare NHS Trust, Cardiff, UK.

The autosomal dominant acute hepatic porphyrias (AHPs), acute intermittent porphyria, hereditary coproporphyria (HCP) and variegate porphyria (VP), are low penetrance adult onset disorders caused by partial deficiency of enzymes of haem biosynthesis. All are associated with acute neurovisceral attacks, which are a consequence of the increased hepatic demand for haem triggered by hormones, stress, drugs or systemic infections which leads to upregulation of the pathway and overproduction of haem precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG). Acute episodes are characterised by severe abdominal pain, nausea, vomiting, hyponatraemia, hypertension and tachycardia, behavioural disturbance and can progress to include seizures, peripheral motor neuropathy and posterior reversible encephalopathy syndrome if undiagnosed and untreated. Read More

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Givosiran for the treatment of acute hepatic porphyria.

Expert Rev Clin Pharmacol 2022 May 11:1-11. Epub 2022 May 11.

Department of Surgical and Medical Sciences for Children and Adults, Internal Medicine Unit, University of Modena and Reggio Emilia, Modena, Italy.

Introduction: Acute hepatic porphyrias (AHPs) are a family of rare inherited disorders characterized by enzyme dysfunctions in the hepatic pathway of heme biosynthesis. In AHPs, accumulation of the neurotoxic porphyrin precursors delta-aminolevulinic acid and porphobilinogen, caused by enhanced activity of hepatic aminolevulinate synthase 1 (ALAS1), is associated with acute, potentially life-threatening neurovisceral attacks. Symptoms during and between attacks dramatically reduce patients' quality of life (QoL). Read More

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Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives.

Orphanet J Rare Dis 2022 04 7;17(1):160. Epub 2022 Apr 7.

Department of Surgical and Medical Sciences for Children and Adults, Internal Medicine Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.

Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Read More

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Flumioxazin, a PPO inhibitor: A weight-of-evidence consideration of its mode of action as a developmental toxicant in the rat and its relevance to humans.

Toxicology 2022 04 30;472:153160. Epub 2022 Mar 30.

Consultant, Harrington House, Brighton BN1 6RE, UK.

Flumioxazin, is a herbicide that has inhibitory activity on protoporphyrinogen oxidase (PPO), a key enzyme in the biosynthetic pathway for heme. Flumioxazin induces anemia and developmental toxicity in rats, including ventricular septal defect and embryofetal death. Studies to elucidate the mode of action (MOA) of flumioxazin as a developmental toxicant and to evaluate its relevance to humans have been undertaken. Read More

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A case report on variegate porphyria after etonogestrel placement.

JAAD Case Rep 2022 Apr 3;22:104-106. Epub 2022 Mar 3.

Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan.

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The Porphyrias.

J Dtsch Dermatol Ges 2022 Mar;20(3):316-331

Department of Dermatology, Venereology and Allergology, University Hospital Göttingen, Göttingen, Germany.

The porphyrias are clinically variable and genetically heterogeneous, predominantly hereditary metabolic diseases, which are caused by a dysfunction of specific enzymes in heme biosynthesis. Here, we provide an overview of the etiopathogenesis, clinic, differential diagnosis, laboratory diagnostics and therapy of these complex metabolic disorders and cover in detail the most common form of porphyria worldwide (porphyria cutanea tarda), the most frequent childhood porphyria (erythropoietic protoporphyria), and the most common neurocutaneous porphyria (variegate porphyria). Read More

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Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy.

Mol Genet Metab Rep 2022 Mar 2;30:100842. Epub 2022 Feb 2.

Helsinki University Hospital, Department of Medicine, Finland.

Background: Acute hepatic porphyria includes four inherited disorders caused by partial deficiencies of enzymes related to the heme biosynthesis. Clinical manifestations include acute attacks, occurring mainly among female patients. This study describes the diversity of acute symptoms, changes in triggering factors and life expectancy among female patients during the past five decades. Read More

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A boy with blistering of sun-exposed skin and finger shortening: the first case of Variegate Porphyria with a novel mutation in protoporphyrinogen oxidase (PPOX) gene in Iran: a case report and literature review.

Ital J Pediatr 2022 Feb 14;48(1):27. Epub 2022 Feb 14.

Preventive Medicine and Public Health Research Center, Psychosocial Health Research Institute, Community and Family Medicine Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Variegate Porphyria (VP) is an inherited rare disorder that is caused by mutations in the protoporphyrinogen oxidase (PPOX) gene. This deficiency is associated with the accumulation of porphyrins and porphyrin precursors in the body, which, in turn, can potentially result in a variety of skin and neurological symptoms. Here, we reported a 7-year-old boy with homozygous VP and novel mutation on PPOX gene. Read More

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February 2022

Risk of primary liver cancer in acute hepatic porphyria patients: A matched cohort study of 1244 individuals.

J Intern Med 2022 Jun 2;291(6):824-836. Epub 2022 Mar 2.

Hepatology Division, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background: The acute hepatic porphyrias (AHP) are associated with a risk of primary liver cancer (PLC), but risk estimates are unclear, and what AHP characteristics that predict PLC risk are unknown. In this register-based, matched cohort study, we assessed the PLC risk in relation to biochemical and clinical porphyria severity, genotype, age, and sex.

Methods: All patients in the Swedish porphyria register with acute intermittent porphyria (AIP), variegate porphyria (VP), or hereditary coproporphyria (HCP) during 1987-2015 were included. Read More

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Molecular characterization of a novel His333Arg variant of human protoporphyrinogen oxidase IX.

Biochem Biophys Res Commun 2022 01 21;588:182-186. Epub 2021 Dec 21.

Laboratory of Structural Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, Vestec, 252 50, Czech Republic. Electronic address:

Variegate porphyria is caused by mutations in the protoporphyrinogen oxidase IX (PPOX, EC 1.3.3. Read More

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January 2022

Heterologous expression and purification of recombinant human protoporphyrinogen oxidase IX: A comparative study.

PLoS One 2021 18;16(11):e0259837. Epub 2021 Nov 18.

Laboratory of Structural Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Czech Republic.

Human protoporphyrinogen oxidase IX (hPPO) is an oxygen-dependent enzyme catalyzing the penultimate step in the heme biosynthesis pathway. Mutations in the enzyme are linked to variegate porphyria, an autosomal dominant metabolic disease. Here we investigated eukaryotic cells as alternative systems for heterologous expression of hPPO, as the use of a traditional bacterial-based system failed to produce several clinically relevant hPPO variants. Read More

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January 2022

ABCB6 polymorphisms are not overly represented in patients with porphyria.

Blood Adv 2022 02;6(3):760-766

Division of Hematology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.

The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Read More

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February 2022

Acute porphyrias - A neurological perspective.

Brain Behav 2021 11 17;11(11):e2389. Epub 2021 Oct 17.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology, Berlin, Germany.

Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic, and peripheral nervous system. Due to their relative rarity and their chameleon-like presentation, delayed diagnosis and misdiagnosis are common. AHPs are genetically inherited disorders that result from heme biosynthesis enzyme deficiencies and comprise four forms: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA-dehydratase porphyria (ALADP). Read More

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November 2021

mRNA-based therapy in a rabbit model of variegate porphyria offers new insights into the pathogenesis of acute attacks.

Mol Ther Nucleic Acids 2021 Sep 19;25:207-219. Epub 2021 May 19.

Hepatology Program, Centre for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain.

Variegate porphyria (VP) results from haploinsufficiency of protoporphyrinogen oxidase (PPOX), the seventh enzyme in the heme synthesis pathway. There is no VP model that recapitulates the clinical manifestations of acute attacks. Combined administrations of 2-allyl-2-isopropylacetamide and rifampicin in rabbits halved hepatic PPOX activity, resulting in increased accumulation of a potentially neurotoxic heme precursor, lipid peroxidation, inflammation, and hepatocyte cytoplasmic stress. Read More

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September 2021

Expert consensus statement on acute hepatic porphyria in Belgium.

Acta Clin Belg 2021 Aug 7:1-7. Epub 2021 Aug 7.

Dienst Maag-Darm-Leverziekten en Metabool Centrum, UZ Leuven, Belgium.

Acute hepatic porphyrias (AHP) are a group of four different rare to ultra-rare, severely debilitating, and sometimes fatal diseases that significantly impact patients' lives: 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). Based on literature estimates, a conservative estimate of the number of AHP patients in Belgium requiring treatment, defined as patients experiencing recurrent attacks and/or chronic debilitating symptoms, is likely limited to 11-34 patients. These patients face a considerable unmet need, as there is currently no pharmaceutical treatment available that effectively prevents attacks and has an impact on other chronic symptoms of the disease. Read More

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The hydrogen bonding network involved Arg59 in human protoporphyrinogen IX oxidase is essential for enzyme activity.

Biochem Biophys Res Commun 2021 06 12;557:20-25. Epub 2021 Apr 12.

State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, National Pesticide Engineering Research Center (Tianjin), Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:

Protoporphyrinogen IX oxidase (PPO) is the last common enzyme in chlorophyll and heme biosynthesis pathways. In human, point mutations on PPO are responsible for the dominantly inherited disorder disease, Variegate Porphyria (VP). Of the VP-causing mutation site, the Arg59 is by far the most prevalent VP mutation residue identified. Read More

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Clinical, biochemical, and genetic characterization of acute hepatic porphyrias in a cohort of Argentine patients.

Mol Genet Genomic Med 2021 05 25;9(5):e1059. Epub 2021 Mar 25.

Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Hospital de Clínicas José de San Martín, CONICET-UBA, Buenos Aires, Argentina.

Background: Acute Hepatic Porphyrias (AHPs) are characterized by an acute neuroabdominal syndrome including both neuropsychiatric symptoms and neurodegenerative changes. Two main hypotheses explain the pathogenesis of nervous system dysfunction: (a) the ROS generation by autooxidation of 5-aminolevulinic acid accumulated in liver and brain; (b) liver heme deficiency and in neural tissues that generate an oxidative status, a component of the neurodegenerative process.

Methods: We review results obtained from Acute Intermittent Porphyria (AIP) and Variegate Porphyria (VP) families studied at clinical, biochemical, and molecular level at the CIPYP in Argentina. Read More

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Acute Variegate Porphyria in a Professional Bodybuilder after Starting a High-protein Diet and Treatment with Testosterone.

Acta Derm Venereol 2021 Mar 11;101(3):adv00412. Epub 2021 Mar 11.

Department of Dermatology, University Hospital, Ruprecht-Karls-University of Heidelberg, DE-69120 Heidelberg, Germany.

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Greater disease burden of variegate porphyria than hereditary coproporphyria: An Israeli nationwide study of neurocutaneous porphyrias.

Mol Genet Metab Rep 2021 Mar 13;26:100707. Epub 2021 Jan 13.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

Hereditary coproporphyria (HCP) and variegate porphyria (VP) are referred to as neurocutaneous porphyrias (NCP). Data concerning their systemic presentation are limited and no direct attempt of comparison of the two has ever been made. Our aim was to describe the type and frequency of systemic manifestations of NCPs in Israeli patients. Read More

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Variegate Porphyria Triggered by Acute Hepatitis A Infection.

Eur J Case Rep Intern Med 2020 22;7(12):001688. Epub 2020 Sep 22.

Department of Dermatology, Mater Dei Hospital, Msida, Malta.

Background: Variegate porphyria (VP) is a rare disorder of haem biosynthesis. We report a novel association with hepatitis A infection.

Patient And Methods: A 31-year-old man was diagnosed with acute hepatitis A infection. Read More

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September 2020

Clinical features of genetic cutaneous porphyrias in Israel: A nationwide survey.

Photodermatol Photoimmunol Photomed 2021 May 20;37(3):236-242. Epub 2020 Dec 20.

Division of Dermatology, Photodermatosis Service, Rabin Medical Center, Petah Tikva, Israel.

Background: There are three major types of genetic cutaneous porphyrias (GCP): erythropoietic protoporphyria (EPP), variegate porphyria (VP), and hereditary coproporphyria (HCP). Scarce data are available regarding their impact on patients' quality of life in the Mediterranean region.

Purpose: To describe the cutaneous features of GCP in Israel. Read More

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Comparative characterization of sun exposed and sun protected skin-derived mesenchymal-like stem cells in variegate porphyria and healthy individuals.

Photodermatol Photoimmunol Photomed 2021 May 11;37(3):202-213. Epub 2020 Dec 11.

Faculty of Medicine, Dermatology Department, American University of Beirut, Beirut, Lebanon.

Background And Purpose: We hypothesized that upon sun exposure, a sub-population of primary skin-derived mesenchymal-like cells is deleteriously affected and thus contribute to the chronic inflammatory state in autosomal recessive variegate porphyria patients. The aim of this study was to isolate and characterize the mesenchymal-like stem cells from different areas of the skin in a porphyria patient (sun exposed, SE, and sun protected, SP) and to compare them with cells from a healthy individual.

Methods: The proliferation rate and the migration ability of SE and SP cells were evaluated in the presence of an antioxidant compound, N-acetylcysteine. Read More

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Novel PPOX exonic mutation inducing aberrant splicing in a patient with homozygous variegate porphyria.

Clin Chim Acta 2021 Jan 4;512:117-120. Epub 2020 Nov 4.

Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address:

Introduction: Variegate porphyria (VP; OMIM 176200) is one of the acute hepatic porphyrias, and it is characterized by the partial deficiency of protoporphyrinogen oxidase (PPOX). The unusual homozygous variant with mutations on both alleles of PPOX is distinguished with general heterozygous VP by several typical points such as severe defect in PPOX enzyme activity, early onset of photosensitivity before puberty, and skeletal deformity.

Material And Method: In this study, we describe a very rare case of autosomal recessive form of true homozygous VP found in a Chinese patient with consanguineous parents. Read More

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January 2021

Hepatocellular Carcinoma in Acute Hepatic Porphyrias: Results from the Longitudinal Study of the U.S. Porphyrias Consortium.

Hepatology 2021 05 11;73(5):1736-1746. Epub 2020 Dec 11.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.

Background And Aims: The risk for hepatocellular carcinoma (HCC) is increased in acute hepatic porphyrias (AHP). The aim of this study was to explore the clinicopathologic characteristics, outcomes, and frequency of HCC in patients with AHP in the United States.

Approach And Results: This cross-sectional analysis evaluated patients with HCC in a multicenter, longitudinal study of AHP. Read More

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Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad?

Eur J Intern Med 2020 09 31;79:101-107. Epub 2020 May 31.

Unit of Internal Medicine, Department of Medical and Surgical Science for Children and Adults, University of Modena and Reggio Emilia, Italy.

Background: Acute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Read More

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September 2020

Two new mutations in the PPOX gene in a patient with variegate porphyria.

J Dtsch Dermatol Ges 2020 Apr 4;18(4):381-383. Epub 2020 Apr 4.

Servicio de Inmunología, Unidad de Gestión Clínica de Hematología, Inmunología y Genética, Hospital Universitario Puerta del Mar, Cádiz, Spain.

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Sick leave, disability, and mortality in acute hepatic porphyria: a nationwide cohort study.

Orphanet J Rare Dis 2020 02 21;15(1):56. Epub 2020 Feb 21.

Norwegian Organisation for Quality Improvement of Laboratory Examinations (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway.

Background: Acute hepatic porphyria (AHP) consists of three rare metabolic disorders. We investigated the risk of long-term sick leave, disability pension, and premature death in individuals with AHP compared to the general population.

Methods: In a nationwide cohort study from 1992 to 2017, records of 333 persons (total person-years = 6728) with a confirmed AHP diagnosis were linked to several national compulsory registries (reference population = 5,819,937). Read More

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February 2020

Penetrance and predictive value of genetic screening in acute porphyria.

Mol Genet Metab 2020 05 10;130(1):87-99. Epub 2020 Feb 10.

Helsinki University Hospital, Department of Medicine, Finland. Electronic address:

Objective: Penetrance, predictive value and female patients' perspectives on genetic testing were evaluated among Finnish patients with acute porphyria. We conducted a retrospective study to evaluate prognosis among at-risk female family members depending on the primary method of diagnosis.

Methods: The penetrance was calculated among 23 genetically heterogeneous families selected from the Finnish porphyria registry (n = 515, AIP 333; VP 182). Read More

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Acute porphyrias: a German monocentric study of the biochemical, molecular genetic, and clinical data of 62 families.

Ann Hematol 2019 Dec 19;98(12):2683-2691. Epub 2019 Nov 19.

EPNET Clinical Center Munich, Hematology Oncology Center and Ludwig Maximilians University Munich, Zweibrückenstr.2, 80331, Munich, Germany.

In Germany, analyses of clinical and laboratory features of patients with acute porphyrias are only available for hereditary coproporphyria (HCP) but not with other acute porphyrias, acute intermittent porphyria (AIP) and variegate porphyria (VP). The aim of the study was to analyze a large cohort of patients with particular focus upon quality of life aspects. Sixty-two individuals from separate families with acute porphyrias (57 AIP, 5 VP) were included into an observational study collecting biochemical, genetic, and clinical data. Read More

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December 2019