scholarly journals The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase.

1975 ◽  
Vol 56 (3) ◽  
pp. 661-667 ◽  
Author(s):  
J P Kushner ◽  
D P Steinmuller ◽  
G R Lee
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Uroporphyrinogen Decarboxylase

scholarly journals Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria

1983 ◽  
Vol 214 (1) ◽  
pp. 145-151 ◽  
Author(s):  
H De Verneuil ◽  
S Sassa ◽  
A Kappas
Keyword(s):  
Polychlorinated Biphenyl ◽  
Porphyria Cutanea Tarda ◽  
Metabolic Activation ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase ◽  
Simultaneous Treatment ◽  
Synergistic Response ◽  
Low Levels ◽  
Tetrachlorodibenzo P Dioxin

Treatment of cultured chick embryo hepatocytes with phenobarbital, polychlorinated biphenyl compounds and 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased delta-aminolaevulinate synthase and decreased uroporphyrinogen decarboxylase activities and porphyrin accumulation; uroporphyrin and heptacarboxyporphyrin predominated. Iron had no effect on these changes. Simultaneous treatment of cultures with dioxin and phenobarbital produced a synergistic response in delta-aminolaevulinate synthase induction, uroporphyrinogen decarboxylase inhibition and porphyrin accumulation. These data suggest that an inhibitor of uroporphyrinogen decarboxylase may be generated in the liver from polychlorinated biphenyl compounds or dioxin by metabolic activation. Additionally these findings bear on the postulated role of these and related chemicals in determining the low levels of uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients.

scholarly journals Role of therapeutic phlebotomy in management of case of porphyria cutanea tarda (PCT) admitted in tertiary care hospital Vadodara  

2020 ◽  
Vol 8 (1) ◽  
pp. 4-6
Author(s):  
Ashu Dogra
Keyword(s):  
Aminolevulinic Acid ◽  
Tertiary Care Hospital ◽  
Porphyria Cutanea Tarda ◽  
Tertiary Care ◽  
Skin Lesions ◽  
Clinical Feature ◽  
Care Hospital ◽  
Skin Symptoms ◽  
Characteristic Clinical Feature

Porphyria cutanea tarda is the most frequent type of Porphyria worldwide & presents with skin symptoms mainly. Porphyrias can affect peripheral, autonomic and central nervous system. In Porphyria conditions there is accumulation of heme precursors 5 Aminolevulinic acid, Porphobilinogen and porphyrins which are associated with characteristic clinical feature with acute neurovisceral attacks and skin lesions. This case report summarizes Case of PCT that was successfully managed with Therapeutic Phlebotomy.

Sight-threatening progressive corneo-scleral involvement in porphyria cutanea tarda

2021 ◽  
Vol 14 (10) ◽  
pp. e245160
Author(s):  
Sonali Prasad ◽  
Vidhata Vidhata ◽  
Subhash Prasad
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Clinical Manifestations ◽  
Ocular Involvement ◽  
Slit Lamp ◽  
Uroporphyrinogen Decarboxylase ◽  
Progressive Loss ◽  
The Right ◽  
Lost To Follow Up ◽  
Test Serum

Porphyria cutanea tarda is the most common type of porphyria. It is associated with a deficiency of uroporphyrinogen decarboxylase enzyme responsible for heme synthesis. Clinical manifestations are predominantly dermatological and very rarely present with ocular involvement. Although scleral thinning in the interpalpebral area is a well-documented entity, sight-threatening corneal involvement is rarely described. We, herein report a case of a 58-year-old man who presented with ocular surface dryness, photophobia and mild redness. Slit-lamp biomicroscopy revealed corneo-scleral thinning in both eyes. The diagnosis was confirmed with a urine porphyrin test, serum iron and serum ferritin levels. We started him on conservative management after which he was lost to follow-up. He presented again after 6 years with total corneal opacification and progressive loss of vision in the right eye.

Complex pattern of alternative splicing in the normal uroporphyrinogen decarboxylase gene: implications for diagnosis of familial porphyria cutanea tarda

1994 ◽  
Vol 40 (10) ◽  
pp. 1884-1889 ◽  
Author(s):  
J F McManus ◽  
C G Begley ◽  
S Ratnaike
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Splice Acceptor ◽  
Uroporphyrinogen Decarboxylase ◽  
Consensus Sequences ◽  
Normal Individuals ◽  
Intron 1 ◽  
Donor And Acceptor ◽  
Multiple Alternative

Abstract We describe multiple alternative transcripts of uroporphyrinogen decarboxylase mRNA in normal individuals and patients with familial porphyria cutanea tarda. mRNA was reverse-transcribed, subjected to the polymerase chain reaction, and analyzed for nucleotide sequence. Seven different transcripts were characterized, and a cryptic splice acceptor site was identified in intron 1. In all mRNAs the exons abutted at previously defined exon boundaries. Characterization of the splice junctions in the genomic DNA showed that splice donor and acceptor sequences complied with the consensus sequences for these sites except for the splice acceptor sequences of exons 3 and 10. THese deviations were present in two normal individuals and one patient with familial porphyria cutanea tarda and were thus unable to explain the multiple aberrant uroporphyrinogen decarboxylase transcripts. We conclude that apparent deletions observed in transcripts derived from the uroporphyrinogen decarboxylase gene in patients with familial porphyria cutanea tarda should be interpreted with caution.

Familial Porphyria Cutanea Tarda: Hybridization Analysis of the Uroporphyrinogen Decarboxylase Locus

1988 ◽  
Vol 38 (5) ◽  
pp. 283-286 ◽  
Author(s):  
Joanna L. Hanseri ◽  
Peter O’Connell ◽  
Marc Romana ◽  
Paul-Henri Romeo ◽  
James P. Kushner
Keyword(s):  
Porphyria Cutanea Tarda ◽  
Hybridization Analysis ◽  
Uroporphyrinogen Decarboxylase

scholarly journals The role of the Ah locus in hexachlorobenzene-induced porphyria. Studies in congenic C57BL/6J mice

1988 ◽  
Vol 254 (1) ◽  
pp. 245-254 ◽  
Author(s):  
M E Hahn ◽  
T A Gasiewicz ◽  
P Linko ◽  
J A Goldstein
Keyword(s):  
Urinary Excretion ◽  
Causative Factor ◽  
Ah Receptor ◽  
Lipid Levels ◽  
Uroporphyrinogen Decarboxylase ◽  
Hepatic Lipid ◽  
Congenic Strains ◽  
Cytosolic Protein ◽  
Hepatic Microsomes

The role of the Ah locus in hexachlorobenzene (HCB)-induced porphyria and the possible involvement of P-450 cytochromes P(1)450 and P(3)450 in the pathogenesis of this disease were investigated in two congenic strains of C57BL/6J mice that differ only at this locus. Female B6-Ahb mice (Ah receptor: approximately 30-70 fmol/mg of cytosolic protein) and B6-Ahd mice (Ah receptor: undetectable) were pretreated with iron (500 mg/kg) and then fed a diet containing 0 or 200 p.p.m. of HCB for up to 17 weeks. Mice from the two strains consumed similar amounts of HCB. Urinary excretion of porphyrins was increased after 7 weeks of HCB treatment in B6-Ahb mice, and after 15 weeks was over 200 times greater than that of mice given iron only. In B6-Ahd mice, porphyrin excretion did not begin to increase until after 13 weeks, and after 15 weeks was only six times greater than that of controls. Similar differences were seen in the 15-week hepatic porphyrin concentrations (B6-Ahb: 1110 +/- 393; B6-Ahd: 17.6 +/- 14.5; controls: approximately 0.20 nmol/g). Uroporphyrinogen decarboxylase (EC 4.1.1.37) activity was diminished by 70 and 20% in B6-Ahb B6-Ahd mice respectively after 15 weeks of treatment with HCB. Cytochromes P(1)450 and P(3)450 were measured in hepatic microsomes (microsomal fractions) by radioimmunoassay and immunoblotting, using antisera raised against the orthologous rat isoenzymes P450c and P450d. HCB induced small amounts of a protein recognized by anti-P450c (P(1)450) in B6-Ahd mice, but not in B6-Ahd mice. Relatively large amounts of a protein recognized by anti-P450d (P(3)450) were induced in both strains, but to a somewhat greater extent in the B6-Ahb mice. The hepatic accumulation of HCB at 15 weeks was greater in B6-Ahb than in B6-Ahd mice, in association with elevated hepatic lipid levels in the former strain. The results of this experiment indicate that the Ah locus influences the susceptibility of C57BL/6J mice to HCB-induced porphyria and are consistent with the suggestion that the sustained induction of P(3)450 and/or P(1)450 may be a causative factor in the development of this disease.

A Retrospective Review of the Management of Patients with Porphyria Cutanea Tarda At a Tertiary Care Centre

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5290-5290
Author(s):  
Jovana Yudin ◽  
Farzana R. Bacchus ◽  
Mark A. Crowther
Keyword(s):  
Clinical Remission ◽  
Conflicts Of Interest ◽  
Porphyria Cutanea Tarda ◽  
Tertiary Care ◽  
Sun Exposure ◽  
Tertiary Care Centre ◽  
Uroporphyrinogen Decarboxylase ◽  
Skin Symptom ◽  
Skin Fragility ◽  
Biochemical Remission

Abstract 5290 Porphyria Cutanea Tarda (PCT) is caused by a deficiency in uroporphyrinogen decarboxylase, an enzyme in the heme biosynthesic pathway. This leads to an excess of porphyrins, which cause blistering and skin fragility on sun exposure. The goals of treatment are iron depletion and reduction of plasma porphyrins to ameliorate skin symptoms. We reviewed the management of all PCT patients at St. Joseph's Hospital followed by the Hematology service, with the objective of describing their treatment course and its efficacy. The type of treatment received as well as the number and volume of phlebotomies were recorded. Outcomes of interest were skin symptom resolution (clinical remission) and biochemical remission, as measured by serum ferritin. Target ferritin was set at 30–50 μg/L. A total of 18 patients with PCT met our inclusion criteria; 14 males and 4 females. Three patients had the familial subtype of PCT while 15 had the sporadic form. Precipitants included alcohol, hepatitis C, hemochromatosis and estrogens. All patients received phlebotomy and three received hydroxychloroquine. Most patients were referred and initially diagnosed by dermatologists. The total volume of phlebotomies per patient ranged from 750–9500 mL for resolution of cutaneous symptoms which was achieved in 75% of patients. At the end of the study period, 15/18 (83%) patients were in clinical remission and 12/18 (67%) were in biochemical remission. Follow-up of PCT patients by a hospital hematology service allows for symptomatic control and biochemical remission in the vast majority of patients through the use of phlebotomy and occasionally hydroxychloroquine. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document