Porphyrias: A 2015 update

Karim, Zoubida; Lyoumi, Saı̈d; Nicolas, Gaël; Deybach, Jean‐Charles; Gouya, Laurent; Puy, Hervé

doi:10.1016/j.clinre.2015.05.009

Cited by 138 publications

(163 citation statements)

References 64 publications

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“…Early studies on the uroporphyrinogen decarboxylase enzyme mechanism focused on the order of decarboxylation and were conducted largely on the metazoan form of the enzyme. The rationale for this choice was the known linkage between the disease porphyria cutanea tarda (PCT) and diminished UROD activity levels (194). An excellent review of early chemically based studies by Jackson's group (195) is available, which outlines the experiments that helped to determine the stepwise decarboxylations that start with the D ring and proceed clockwise to the A, B, and, finally, C rings (196).…”

Section: Two Branches To Synthesize Protoheme Uroporphyrinogen Decarbmentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

258

335

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SUMMARY The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized.

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Section: Two Branches To Synthesize Protoheme Uroporphyrinogen Decarbmentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

258

335

View full text Add to dashboard Cite

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“…The main clinical manifestations include skin photosensitivity, skin burning, itching with subsequent cutaneous signs such as swelling and redness after visible light exposure, while blisters are sparse. Some patients may have cholestatic hepatic disease, even leading to liver failure (Karim et al, 2015). Because of its rarity and the non-specificity of clinical symptoms, it is difficult to make the diagnosis of EPP and treat the patients early.…”

Section: Introductionmentioning

confidence: 99%

Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review

Long

Wang

Chen

et al. 2016

J. Zhejiang Univ. Sci. B

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Erythropoietic protoporphyria (EPP), an autosomal dominant disease, is caused by partial deficiency of ferrochelatase (FECH), which catalyzes the terminal step of heme biosynthesis because of loss-of-function mutations in the FECH gene. To date, only a few cases have been described in Asia. In this study, we describe the clinical features of two Chinese patients with EPP, with diagnosis confirmed by the increase of free protoporphyrin in erythrocytes, detection of plasma fluorescence peak at 630-634 nm, and analysis of FECH gene mutations. Using gene scanning, we identified a small deletion in the FECH gene (c.973 delA) in one proband (patient A) and a pathogenic FECH mutation (c.1232 G>T) in the other (patient B) and also observed some nucleotide variations (c.798 C>G, c.921 A>G, IVS1−23 C>T, IVS3+23 A>G, IVS9+35 C>T, and IVS3−48 T>C) in these patients. The family pedigree of patient A was then established by characterization of the genotype of the patient's relatives. We also analyzed the potential perniciousness of the missense mutation with bioinformatic software, Polyphen and Sift. In summary, Chinese EPP patients have similar manifestations to those of Caucasians, and identification of the Chinese FECH gene mutations expands the FECH genotypic spectrum and may contribute to genetic counseling.

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“…Its prevalence is 2-3 cases per 100000 persons per year [7]. Although the disease shows an autosomal dominant inheritance, genetic penetrance is low [8]. The most common presenting symptom of AIP is abdominal pain lasting from hours to days.…”

Section: Discussionmentioning

confidence: 99%

Secret Underlying Unexplained Abdominal Pain, Neurological Symptoms and Intermittent Hypertension: Acute Intermittent Porphyria

et al. 2017

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A 21-year-old female patient with abdominal pain, vomiting and constipation was admitted to the hospital with the possible diagnosis of diabetic ketoacidosis. Due to increased abdominal pain and constipation the patient underwent a surgery with the diagnosis of ileus. However, no pathological findings were found in the abdominal organs apart from serous fluid in the abdominal cavity. The patient became hypertensive, tachycardic and had an episode of seizures postoperatively. Neurological manifestations with unexplained abdominal pain indicated a diagnosis of acute intermittent porphyria (AIP). Acute intermittent porphyria diagnosis is based on elevated urinary δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels as well as hydroxymethylbilane synthase (HMBS) IVS13-2 A>G heterozygous mutation. Familial Mediterranean Fever (FMF) gene mutations were not confirmed. Porphyria should be considered in the differential diagnosis of patients with recurrent abdominal pain, neurological symptoms and lack of FMF gene polymorphism.

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Porphyrias: A 2015 update

Cited by 138 publications

References 64 publications

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Identification of FECH gene multiple variations in two Chinese patients with erythropoietic protoporphyria and a review

Secret Underlying Unexplained Abdominal Pain, Neurological Symptoms and Intermittent Hypertension: Acute Intermittent Porphyria

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