10,679 results match your criteria Porphyria Hereditary Coproporphyria

Within- and between-subject biological variation data for tumor markers based on the European Biological Variation Study.

Clin Chem Lab Med 2021 May 10. Epub 2021 May 10.

EFLM Working Group on Biological Variation, Milan, Italy.

Objectives: Reliable biological variation (BV) data are required for the clinical use of tumor markers in the diagnosis and monitoring of treatment effects in cancer. The European Biological Variation Study (EuBIVAS) was established by the EFLM Biological Variation Working Group to deliver BV data for clinically important measurands. In this study, EuBIVAS-based BV estimates are provided for cancer antigen (CA) 125, CA 15-3, CA 19-9, carcinoembryonic antigen, cytokeratin-19 fragment, alpha-fetoprotein and human epididymis protein 4. Read More

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Porphyria Cutanea Tarda.

Mayo Clin Proc 2021 May;96(5):1248-1249

Division of Dermatopathology, Department of Dermatology, Mayo Clinic, Rochester, MN. Electronic address:

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Acitretin mitigates uroporphyrin-induced bone defects in congenital erythropoietic porphyria models.

Sci Rep 2021 May 5;11(1):9601. Epub 2021 May 5.

Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, 08854, USA.

Congenital erythropoietic porphyria (CEP) is a rare genetic disorder leading to accumulation of uro/coproporphyrin-I in tissues due to inhibition of uroporphyrinogen-III synthase. Clinical manifestations of CEP include bone fragility, severe photosensitivity and photomutilation. Currently there is no specific treatment for CEP, except bone marrow transplantation, and there is an unmet need for treating this orphan disease. Read More

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Erythropoietic protoporphyria: time to prodrome, the warning signal to exit sun exposure without pain-a patient-reported outcome efficacy measure.

Genet Med 2021 May 3. Epub 2021 May 3.

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

Purpose: Patients with erythropoietic protoporphyria (EPP), a severe painful photodermatosis, experience prodromal sensations when exposed to sunlight, which are the "warning signals" to exit the sun, as prolonged exposure causes an excruciatingly painful phototoxic attack. The unique prodromal cutaneous sensations are reversible and differ from the severe burning pain attack lasting 2-7 days. Previously, afamelanotide treatment was studied using time to pain or time outside as primary outcome measures. Read More

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Drug Metab Dispos 2021 May 3. Epub 2021 May 3.

Drug Metabolism and Pharmacokinetics, Alnylam Pharmaceuticals Inc., United States

Givosiran is a N-acetylgalactosamine (GalNAc)-conjugated RNA interference (RNAi) therapeutic that targets 5'-aminolevulinate synthase 1 () messenger RNA (mRNA) in the liver and is currently marketed for the treatment of acute hepatic porphyria (AHP). Herein, nonclinical pharmacokinetic (PK) and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Givosiran was completely absorbed after subcutaneous (SC) administration with relatively short plasma elimination t (less than 4 hours). Read More

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Porphyria: awareness is the key to diagnosis!

Acta Clin Belg 2021 May 3:1-7. Epub 2021 May 3.

Department of General Internal Medicine, KU Leuven, Leuven, Belgium.

Porphyrias are disorders of the haem biosynthesis which are encountered infrequently and which often present themselves atypically as a combination of gastrointestinal, neurologic and/or dermatologic symptoms. Although they are primarily caused by enzyme defects, inheritance patterns are mostly not evident. Considering all of these characteristics, it is not surprising that there is a long delay between the onset of symptoms and the diagnosis of the disease, with as possible consequences impaired quality of life, irreversible neurologic damage and even death. Read More

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Development of siRNA Therapeutics for the Treatment of Liver Diseases.

Methods Mol Biol 2021 ;2282:57-75

Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

Small interfering RNA (siRNA)-based therapeutics holds the promise to treat a wide range of human diseases that are currently incurable using conventional therapies. Most siRNA therapeutic efforts to date have focused on the treatment of liver diseases due to major breakthroughs in the development of efficient strategies for delivering siRNA drugs to the liver. Indeed, the development of lipid nanoparticle-formulated and GalNAc-conjugated siRNA therapeutics has resulted in recent FDA approvals of the first siRNA-based drugs, patisiran for the treatment of hereditary transthyretin amyloidosis and givosiran for the treatment of acute hepatic porphyria, respectively. Read More

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January 2021

Patient and caregiver experiences of living with acute hepatic porphyria in the UK: a mixed-methods study.

Orphanet J Rare Dis 2021 Apr 26;16(1):187. Epub 2021 Apr 26.

Alnylam Pharmaceuticals, Cambridge, MA, USA.

Background: This study used quantitative and qualitative research methods to analyze how acute hepatic porphyria (AHP) affects patients with varying annualized porphyria attack rates. The overall impact of AHP on patients and caregivers, including their quality of life, was explored. The nature and treatment of acute attacks, experiences of long-term heme arginate treatment and access to other appropriate treatment, and the extent of and treatment for chronic symptoms were also investigated within this study. Read More

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Givosiran: A Review in Acute Hepatic Porphyria.

Yahiya Y Syed

Drugs 2021 Apr 19. Epub 2021 Apr 19.

Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.

Givosiran (Givlaari) is an δ-aminolevulinic acid synthase 1 (ALAS1)-directed small interfering RNA (siRNA) approved for the treatment of acute hepatic porphyria (AHP). In the phase 3 ENVISION trial, givosiran significantly reduced the annualized rate of composite porphyria attacks (i.e. Read More

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Biochemical Diagnosis of Acute Hepatic Porphyria: Updated Expert Recommendations for Primary Care Physicians.

Am J Med Sci 2021 Apr 15. Epub 2021 Apr 15.

Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Acute hepatic porphyria (AHP) is a group of rare, metabolic diseases where patients can experience acute neurovisceral attacks, chronic symptoms, and long-term complications. Diagnostic biochemical testing is widely available and effective, but a substantial time from symptom onset to diagnosis often delays treatment and increases morbidity. A panel of laboratory scientists and clinical AHP specialists collaborated to produce recommendations on how to enhance biochemical diagnosis of AHP in the USA. Read More

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Dysregulation of homocysteine homeostasis in acute intermittent porphyria patients receiving heme arginate or givosiran.

J Inherit Metab Dis 2021 Apr 16. Epub 2021 Apr 16.

Norwegian Porphyria Centre (NAPOS), Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hydroxymethylbilane synthase gene. Previous studies have reported increased levels of plasma total homocysteine (tHcy) in symptomatic AIP patients. In this study, we present long-term data for tHcy and related parameters for an AIP patient cohort (n = 37) in different clinical disease-states. 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 Apr 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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Congenital erythropoietic porphyria: A case series of a rare uroporphyrinogen III synthase gene mutation in Nepalese patients.

JAAD Case Rep 2021 Apr 25;10:102-106. Epub 2021 Feb 25.

Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.

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Targeted urine metabolomics with a graphical reporting tool for rapid diagnosis of inborn errors of metabolism.

J Inherit Metab Dis 2021 Apr 11. Epub 2021 Apr 11.

Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.

The current diagnostic work-up of inborn errors of metabolism (IEM) is rapidly moving toward integrative analytical approaches. We aimed to develop an innovative, targeted urine metabolomics (TUM) screening procedure to accelerate the diagnosis of patients with IEM. Urinary samples, spiked with three stable isotope-labeled internal standards, were analyzed for 258 diagnostic metabolites with an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) configuration run in positive and negative ESI modes. Read More

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Quantification of different iron forms in the aceruloplasminemia brain to explore iron-related neurodegeneration.

Neuroimage Clin 2021 Apr 3;30:102657. Epub 2021 Apr 3.

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

Aims: Aceruloplasminemia is an ultra-rare neurodegenerative disorder associated with massive brain iron deposits, of which the molecular composition is unknown. We aimed to quantitatively determine the molecular iron forms in the aceruloplasminemia brain, and to illustrate their influence on iron-sensitive MRI metrics.

Methods: The inhomogeneous transverse relaxation rate (R*) and magnetic susceptibility obtained from 7 T MRI were combined with Electron Paramagnetic Resonance (EPR) and Superconducting Quantum Interference Device (SQUID) magnetometry. Read More

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The acute hepatic porphyrias.

Bruce Wang

Transl Gastroenterol Hepatol 2021 5;6:24. Epub 2021 Apr 5.

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

The acute hepatic porphyrias (AHP) are a group of four inherited diseases of heme biosynthesis. They present with similar severe, episodic, acute neurovisceral symptoms due to abnormally elevated levels of porphyrin precursors delta-aminolevulinic acid (ALA). Recently genetic screening indicates that the prevalence of mutation carrier state is more common than previously thought, occurring in 1 in 1,500, though the clinical penetrance of symptomatic AHP is low at ~1%. Read More

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Two Zn(II)-based Coordination Polymers: Treatment Activity on Chronic Periodontitis by Inhibiting the Relative Expression of the Porphyria gingivalis Survival Gene.

J Oleo Sci 2021 ;70(4):541-548

Department of Periodontology, Qingdao Stomatological Hospital.

Two mixed-ligand complexes on the basis of L ligand [L = 3,6-bis(imidazol-1-yl)pyridazine] have been prepared under the solvothermal reaction conditions via the Zn(II) salts reacting with the ligands of L in the existence of two positional isomerous carboxylic acid ligands and their chemical formula respectively are [Zn(L)(1,2-BDC)(μ-OH)] (1, 1,2-HBDC = 1,2-benzenedicarboxylic acid ) and {[Zn(L)(1,3-HBDC) (1,3-BDC)(μ-OH)]·ClO·3HO} (2, 1,3-HBDC = 1,3-benzenedicarboxylic acid). The inhibitory influence of the two compounds against the inflammatory response in periodontium was evaluated by measuring the inflammatory cytokines releasing with ELISA detection kit. The results of ELISA assay indicated that compound 1 showed much stronger inhibitory influences than compound 2 against the inflammatory cytokines releasing. Read More

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January 2021

High Prevalence of Insulin Resistance in Asymptomatic Patients with Acute Intermittent Porphyria and Liver-Targeted Insulin as a Novel Therapeutic Approach.

Biomedicines 2021 Mar 5;9(3). Epub 2021 Mar 5.

Hepatology Program, Cima Universidad de Navarra, 31008 Pamplona, Spain.

Acute porphyria attacks are associated with the strong up-regulation of hepatic heme synthesis and over-production of neurotoxic heme precursors. First-line therapy is based on carbohydrate loading. However, altered glucose homeostasis could affect its efficacy. Read More

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Porphyric neuropathy.

Muscle Nerve 2021 Mar 31. Epub 2021 Mar 31.

Section on Gastroenterology & Hepatology, Department of Internal Medicine, Wake Forest Baptist health, Winston Salem, North Carolina, USA.

Acute hepatic porphyrias are inherited metabolic disorders that may present with polyneuropathy, which if not diagnosed early can lead to quadriparesis, respiratory weakness, and death. Porphyric neuropathy is an acute to subacute motor predominant axonal neuropathy with a predilection for the upper extremities and usually preceded by a predominantly parasympathetic autonomic neuropathy. The rapid progression and associated dysautonomia mimic Guillain-Barré syndrome but are distinguished by the absence of cerebrospinal fluid albuminocytologic dissociation, progression beyond 4 wk, and associated abdominal pain. Read More

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Muscle atrophy induced by overexpression of ALAS2 is related to muscle mitochondrial dysfunction.

Skelet Muscle 2021 Mar 30;11(1). Epub 2021 Mar 30.

Institute of Translational Medicine, National and Local Joint Engineering Laboratory of High-through Molecular Diagnostic Technology, the First People's Hospital of Chenzhou, The First Affiliated Hospital of Xiangnan University, Chenzhou, 423000, China.

Background: ALAS2 (delta-aminolevulinate synthase 2) is one of the two isoenzymes catalyzing the synthesis of delta-aminolevulinic acid (ALA), which is the first precursor of heme synthesis. ALAS2-overexpressing transgenic mice (Tg mice) showed syndrome of porphyria, a series of diseases related to the heme anabolism deficiency. Tg mice showed an obvious decrease in muscle size. Read More

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Case Report: A Possible Case of Congenital Erythropoietic Porphyria in a Gir Calf: A Clinical, Pathological, and Molecular Approach.

Front Vet Sci 2021 12;8:632762. Epub 2021 Mar 12.

Veterinary Pathology Laboratory, University of Brasília, Campus Darcy Ribeiro, Brasília, Brazil.

Congenital erythropoietic porphyria (CEP) is a rare hereditary autosomal recessive disease which has never been reported in Zebu cattle. A 3-day-old Gir calf showed teeth discoloration, fever, dehydration, and dyspnea. The main gross findings were pink-colored teeth, red-brown periosteum and bone marrow, and a fluorescent bright pink coloration of the bone marrow and articular surfaces under ultraviolet light. Read More

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Novel treatment options for acute hepatic porphyrias.

Bruce Wang

Curr Opin Gastroenterol 2021 May;37(3):194-199

Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Purpose Of Review: Acute hepatic porphyrias (AHP) are a group of rare diseases that are characterized by episodic acute neurovisceral pain episodes caused by abnormal accumulation of the neurotoxic porphyrin precursor delta-aminolevulinic acid (ALA). Patient with frequent recurrent acute attacks have been difficult to treat and these patients sometimes require liver transplantation. Recent developments in small interfering RNA (siRNA)-based therapy led to the development of an effective prophylactic treatment for patients with frequent recurrent attacks. 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 Mar 25: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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Sex-based differences in and risk factors for metabolic syndrome in adults aged 40 years and above in Northeast China: Results from the cross-sectional China national stroke screening survey.

BMJ Open 2021 Mar 24;11(3):e038671. Epub 2021 Mar 24.

Stroke Center, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China

Objectives: Low levels of income and education are risk factors for metabolic syndrome in the population of Northeast China, which has a high incidence of metabolic syndrome and cardiovascular diseases. This study aimed to determine sex-based differences associated with the prevalence of and risk factors for metabolic syndrome among people older than 40 years in Northeast China; this has not been previously investigated.

Design: This study analysed a portion of the large sample data of the national cross-sectional screening of China from 2016. Read More

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Unusual Pain Disorders - What Can Be Learned from Them?

J Pain Res 2020 15;13:3539-3554. Epub 2021 Mar 15.

Department of Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.

Pain is common in many different disorders and leads to a significant reduction in quality of life in the affected patients. Current treatment options are limited and often result in insufficient pain relief, partly due to the incomplete understanding of the underlying pathophysiological mechanisms. The identification of these pathomechanisms is therefore a central object of current research. Read More

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Repurposing of glycine transport inhibitors for the treatment of erythropoietic protoporphyria.

Cell Chem Biol 2021 Mar 13. Epub 2021 Mar 13.

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address:

Erythropoietic protoporphyria (EPP) is a rare disease in which patients experience severe light sensitivity. It is caused by a deficiency of ferrochelatase (FECH), the last enzyme in heme biosynthesis (HBS). The lack of FECH causes accumulation of its photoreactive substrate protoporphyrin IX (PPIX) in patients' erythrocytes. Read More

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Acute porphyria presenting as abdominal pain in pregnancy.

CMAJ 2021 Mar;193(12):E419-E422

Department of Medicine, University of Ottawa, Ottawa, Ont.

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HPLC methods for choloroquine determination in biological samples and pharmaceutical products.

Daru 2021 Mar 19. Epub 2021 Mar 19.

School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo (FCFRP-USP), Avenida do Café, s/n, Ribeirao Preto, São Paulo, 14040-903, Brazil.

Objective: Review and assess pharmaceutical and clinical characteristics of chloroquine including high-performance liquid chromatography (HPLC)-based methods used to quantify the drug in pharmaceutical products and biological samples.

Evidence Acquisition: A literature review was undertaken on the PubMed, Science Direct, and Scielo databases using the following keywords related to the investigated subject: 'chloroquine', 'analytical methods', and 'HPLC'.

Results: For more than seven decades, chloroquine has been used to treat malaria and some autoimmune diseases, such as lupus erythematosus and rheumatoid arthritis. Read More

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