Update on the Porphyrias
Annu Rev Med. 2023 Aug 4. doi: 10.1146/annurev-med-042921-123602. Online ahead of print.ABSTRACTThe porphyrias are a group of rare diseases, each resulting from a defect in a different enzymatic step of the heme biosynthetic pathway. They can be broadly divided into two categories, hepatic and erythropoietic porphyrias, depending on the primary site of accumulation of heme intermediates. These disorders are multisystemic with variable symptoms that can be encountered by physicians in any specialty. Here, we review the porphyrias and describe their clinical presentation, diagnosis, and management. We discuss novel therapies...
Source: Annual Review of Medicine - August 4, 2023 Category: General Medicine Authors: Amy K Dickey Rebecca Karp Leaf Manisha Balwani Source Type: research
Acute intermittent porphyria: Acute flare-up resolved with givosiran
Med Clin (Barc). 2023 Jul 24:S0025-7753(23)00376-7. doi: 10.1016/j.medcli.2023.06.016. Online ahead of print.NO ABSTRACTPMID:37495504 | DOI:10.1016/j.medcli.2023.06.016 (Source: Medicina Clinica)
Source: Medicina Clinica - July 26, 2023 Category: General Medicine Authors: Andrea Mar ía Balado González Carlos Feijoo-Mass ó Mar ía Del Carmen Navarro-Saez Source Type: research
Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial
Acute hepatic porphyria (AHP) is caused by defects in hepatic heme biosynthesis, leading to disabling acute neurovisceral attacks and chronic symptoms. In ENVISION (NCT03338816), givosiran treatment for 6 months reduced attacks and other disease manifestations, compared with placebo. Here we report data from the 36-month final analysis of ENVISION. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 18, 2023 Category: Gastroenterology Authors: David J. Kuter, Herbert L. Bonkovsky, Susana Monroy, Gayle Ross, Encarna Guill én-Navarro, Maria Domenica Cappellini, Anna-Elisabeth Minder, Ole Hother-Nielsen, Paolo Ventura, Gang Jia, Marianne T. Sweetser, Manish Thapar, for the ENVISION Investigators Source Type: research
Quantitative Analysis of Planarian Pigmentation
Methods Mol Biol. 2023;2680:253-261. doi: 10.1007/978-1-0716-3275-8_16.ABSTRACTThe ommochrome and porphyrin body pigments that give freshwater planarians their brown color are produced by specialized dendritic cells located just beneath the epidermis. During embryonic development and regeneration, differentiation of new pigment cells gradually darkens newly formed tissue. Conversely, prolonged light exposure ablates pigment cells through a porphyrin-based mechanism similar to the one that causes light sensitivity in rare human disorders called porphyrias. Here, we describe a novel program using image-processing algorithms ...
Source: Mol Biol Cell - July 10, 2023 Category: Molecular Biology Authors: Matthew Pittendreigh Kaleigh Powers Meenalosini Vimal Cruz Jason Pellettieri Source Type: research
Quantitative Analysis of Planarian Pigmentation
Methods Mol Biol. 2023;2680:253-261. doi: 10.1007/978-1-0716-3275-8_16.ABSTRACTThe ommochrome and porphyrin body pigments that give freshwater planarians their brown color are produced by specialized dendritic cells located just beneath the epidermis. During embryonic development and regeneration, differentiation of new pigment cells gradually darkens newly formed tissue. Conversely, prolonged light exposure ablates pigment cells through a porphyrin-based mechanism similar to the one that causes light sensitivity in rare human disorders called porphyrias. Here, we describe a novel program using image-processing algorithms ...
Source: Mol Biol Cell - July 10, 2023 Category: Molecular Biology Authors: Matthew Pittendreigh Kaleigh Powers Meenalosini Vimal Cruz Jason Pellettieri Source Type: research
Porphyrias: Uncommon disorders masquerading as common childhood diseases
A Chakraborty, M Muranjan, S Karande, V KharkarJournal of Postgraduate Medicine 2023 69(3):164-171
Porphyrias are a rare group of inborn errors of metabolism due to defects in the heme biosynthetic pathway. The biochemical hallmark is the overproduction of porphyrin precursors and porphyrin species. Afflicted patients present with a myriad of symptoms causing a diagnostic odyssey. Symptoms often overlap with those of common diseases and may be overlooked unless there is heightened clinical suspicion. We are reporting clinical features and diagnostic challenges in four pediatric patients having variegate porphyria, congeni...
Source: Journal of Postgraduate Medicine - July 10, 2023 Category: Internal Medicine Authors: A Chakraborty M Muranjan S Karande V Kharkar Source Type: research
Detect Acute Porphyrias in Emergency Departments (DePorED) – a pilot study
Acute porphyrias (APs) are a group of rare metabolic diseases related to a disturbed heme biosynthesis. Symptoms may first occur as life threatening attacks, comprising abdominal pain and/or variable neuro-psy... (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - June 12, 2023 Category: Internal Medicine Authors: Eva Diehl-Wiesenecker, Sabine Blaschke, Nils Wohmann, Ilja Kubisch, Thomas Stauch, Mona Mainert, Franziska Helm, Sabine von Wegerer, David Pittrow, Jorge Frank, Ulrich St ölzel and Rajan Somasundaram Tags: Research Source Type: research
GSE203437 Transcriptome Profile Analysis Reveals Putative Molecular Mechanisms Of 5-Aminolevulinic Acid Related To Acute Hepatic Porphyrias
This study contributes to revealing molecular mechanisms of ALA potentially associated with the pathogenes is of the clinical manifestations of AHPs. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - May 15, 2023 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Pathogenesis of acute encephalopathy in acute hepatic porphyria
AbstractAcute encephalopathy (AE) can be a manifestation of an acute porphyric attack. Clinical data were studied in 32 patients during AE with or without polyneuropathy (PNP) together with 12 subjects with PNP but no AE, and 17 with dysautonomia solely. Brain neuroimaging was done in 20 attacks during AE, and PEPT2 polymorphisms were studied in 56 subjects, 24 with AE. AE manifested as a triad of seizures, confusion and/or blurred vision. Symptoms lasting 1 –5 days manifested 3–19 days from the onset of an attack. 55% of these patients had acute PNP independent of AE. Posterior reversible encephalopathy syndrome (PR...
Source: Journal of Neurology - April 30, 2023 Category: Neurology Source Type: research
Absorption, metabolism, and excretion of [14C]dersimelagon, an investigational oral selective melanocortin 1 receptor agonist, in preclinical species and healthy volunteers
Dersimelagon (formerly MT-7117) is a novel, orally administered nonpeptide small molecule selective agonist for melanocortin 1 receptor currently being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. Studies evaluating absorption, distribution, metabolism, and excretion (ADME) demonstrated dersimelagon is extensively metabolized to the glucuronide in the liver, which is eliminated in bile, and hydrolyzed to unchanged dersimelagon in the gut. The primary route of excretion was feces. Major metabolites detected in human feces and plasma as we...
Source: Pharmacology Research and Perspectives - April 20, 2023 Category: Drugs & Pharmacology Authors: Minoru Tsuda,
Kei Ogawa,
Tadashi Endou,
Takahiro Goto,
Yuko Ogasawara,
Akihito Ogasawara Tags: ORIGINAL ARTICLE Source Type: research
769 Reduced expression of PPOX, the variegate porphyria gene, causes intrinsic pathological changes to keratinocytes
Variegate porphyria, due to monoallelic mutations in protoporphyrinogen oxidase (PPOX), causes acute visceral attacks and skin photosensitivity, presenting in blistering and skin fragility, a more severe phenotype is seen with rare biallelic mutations. This is due to accumulation of intermediate porphyrins such as 5 ’-aminolevulenic acid (ALA), close to the skin surface that are oxidized by sunlight. Oxidized porphyrins cause oxidative stress and degranulation of mast cells resulting in the release of proteases that cause blistering. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 17, 2023 Category: Dermatology Authors: C.J. Smith, L. Chan, L.A. Metherell Source Type: research
1144 Long-term observation of the clinical and serological findings in three patients with incomplete erythropoietic protoporphyria
Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by both the partial deficiency of ferrochelatase (FECH) and the existence of IVS3-48C in trans to a mutated FECH allele. We previously reported three Japanese patients with a mild phenotype of EPP, which is characterized by for a mild photosensitivity, a slight increase in protoporphyrin (PP) concentration, and the formation of a small number of fluorocytes. These patients have homozygous IVS3-48C polymorphism without causative FECH gene mutations, which can slightly decrease the FECH activity and increase of PP. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 17, 2023 Category: Dermatology Authors: M. Mizawa, T. Makino, T. Shimizu Source Type: research
Severe Abdominal Pain After Bariatric Surgery: Think Twice —Think Porphyria!
(Source: Obesity Surgery)
Source: Obesity Surgery - April 1, 2023 Category: Surgery Source Type: research
Pharmacokinetic ‐pharmacodynamic model of urinary δ‐aminolevulinic acid reduction after givosiran treatment in patients with acute hepatic porphyria
AbstractGivosiran, an RNA interference-based therapeutic, is a recent addition to the limited treatment armamentarium for acute hepatic porphyria (AHP). As a small interfering RNA that is selectively taken up in the liver, both the mechanism and targeted delivery create a complex relationship between givosiran pharmacokinetics (PK) and the pharmacodynamic (PD) response. Using pooled data from phase I –III clinical trials of givosiran, we developed a semimechanistic PK/PD model to describe the relationship between predicted liver and RNA-induced silencing complex concentrations of givosiran and the associated reduction in...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 25, 2023 Category: Drugs & Pharmacology Authors: Jongtae Lee,
Megan Melch,
Gabriel J. Robbie Tags: ARTICLE Source Type: research
