Subject: porphyria


Subject: Iron overload in porphyria cutanea tarda.

       Haematologica 1999 Mar;84(3):248-253

Iron overload in porphyria cutanea tarda.

    Fargion S, Sampietro M, Fiorelli G

      Dipartimento di Medicina Interna, Pad. Granelli, IRCCS
      Policlinico, via F. Sforza 35, 20122 Milan, Italy.
      silvia.fargion@unimi.it

      [Record supplied by publisher]

      BACKGROUND AND OBJECTIVE: Porphyria cutanea tarda (PCT) is a
      disorder of porphyrin metabolism associated with decreased
      activity of uroporphyrinogen decarboxylase (URO-D) in the
      liver. The relevance of iron in the pathogenesis of PCT is
      well established: iron overload is one of the factors that
      trigger the clinical manifestations of the disease and iron
      depletion remains the cornerstone of therapy for PCT. A role
      for genetic hemochromatosis in the pathogenesis of iron
      overload in PCT has been hypothesized in the past but only
      after the recent identification of the genetic defect causing
      hemochromatosis has the nature of this association been
      partially elucidated. This review will outline current
      concepts of the pathophysiology of iron overload in PCT as
      well as recent contributions to the molecular epidemiology of
      hemochromatosis defects in PCT. EVIDENCE AND INFORMATION
      SOURCES: The authors of the present review have a
      long-standing interest in the pathogenesis, etiology and
      epidemiology of iron overload syndromes. Evidence from
      journal articles covered by the Science Citation Index(R) and
      Medline(R) has been reviewed and collated with personal data
      and experience. STATE OF THE ART AND PERPECTIVES: Mild to
      moderate iron overload plays a key role in the pathogenesis
      of PCT. The recent identification of genetic mutations of the
      hemochromatosis gene (HFE) in the majority of patients with
      PCT confirms previous hypotheses on the association between
      PCT and hemochromatosis, allows a step forward in the
      understanding of the pathophysiology of the disturbance of
      iron metabolism in the liver of PCT patients, and provides an
      easily detectable genetic marker which could have a useful
      clinical application. Besides the epidemiological relevance
      of the association between PCT and hemochromatosis, however,
      it remains to be fully understood how iron overload, and in
      particular the cellular modifications of the iron status
      secondary to hemochromatosis mutations, affect the activity
      of URO-D, and how the altered iron metabolism interacts with
      the other two common triggers for PCT and etiological agents
      for the associated liver disease: alcohol and hepatitis
      viruses. The availability of a genetic marker for
      hemochromatosis will allow some of these issues to be
      addressed by studying aspects of porphyrins and iron
      metabolism in liver samples obtained from patients with PCT,
      liver disease of different etiology and different HFE
      genotypes, and by in vitro studies on genotyped cells and
      tissues.

      PMID: 10095256


   
   Gastroenterology 97: 972-81 (1989)[89378676]
   
HLA-linked hemochromatosis alleles in sporadic porphyria cutanea tarda.

   
   
    C. Q. Edwards, L. M. Griffen, D. E. Goldgar, M. H. Skolnick & J. P. Kushner
    
   
   
   Department of Internal Medicine, University of Utah College of
   Medicine, Salt Lake City.
   
   We tested the hypothesis that the hepatic siderosis that characterizes
   sporadic porphyria cutanea tarda is due to the presence of HLA-linked
   hemochromatosis alleles. We studied 21 probands with sporadic
   porphyria cutanea tarda and 135 of their relatives by determining HLA
   haplotypes and measuring transferrin saturation and serum ferritin
   concentration. Liver biopsies were performed in all probands and in
   relatives when appropriate. Seventeen pedigrees were available and
   were studied by both likelihood analysis and by a gene counting
   method. We estimated that 10 of the 17 probands with available living
   relatives possessed at least one hemochromatosis allele. Thirteen of
   the 21 probands (62%) possessed at least one HLA-A3 alloantigen.
   Eighteen of 69 relatives who shared an HLA haplotype with a proband
   (26%) had an elevation of transferrin saturation or serum ferritin
   concentration. Only one first-degree relative not sharing an HLA
   haplotype with a proband had an elevated transferrin saturation or
   serum ferritin concentration. These findings indicate that HLA-linked
   hemochromatosis alleles are far more common in patients with sporadic
   porphyria cutanea tarda than in individuals in the general population
   and may be responsible for the hepatic siderosis associated with most
   cases of sporadic porphyria cutanea tarda.
   
   MeSH Terms:
     * Adult
     * Aged
     * Alleles*
     * Female
     * Ferritin/blood
     * Gene Frequency
     * HLA Antigens/genetics
     * HLA-A Antigens/genetics
     * Hemochromatosis/blood
     * Hemochromatosis/complications
     * Hemochromatosis/genetics
     * Human
     * Linkage (Genetics)*
     * Male
     * Middle Age
     * Pedigree
     * Porphyria/blood
     * Porphyria/complications
     * Porphyria/genetics
     * Skin Diseases/blood
     * Skin Diseases/complications
     * Skin Diseases/genetics
     * Support, U.S. Gov't, P.H.S.
     * Transferrin/analysis
       
   
   
   Substances:
     * Transferrin
     * Ferritin
     * HLA Antigens
     * HLA-A Antigens
     * HLA-A3 Antigen
       
   
     _________________________________________________________________

Subject: porphyria

   
   Toxicol Lett 2001 May 31;122(1):97-102
   
Vitamin E protects against iron-hexachlorobenzene induced porphyria and
formation of 8-hydroxydeoxyguanosine in the liver of C57BL/10ScSn mice.

    Horvath ME, Faux SP, Smith AG, Blazovics A, van der Looij M, Feher J,
    Cheeseman KH
    
   Second Department of Medicine, Semmelweis University Medical School,
   Szentkriralyi u.46 1088, Budapest, Hungary
   
   [Medline record in process]
   
   The effect of vitamin E treatment on total porphyrin content, lipid
   peroxidation (LOOH) and 8-hydroxydeoxyguanosine (8-OHdG) was studied
   in the livers of C57BL/10ScSn mice following hexachlorobenzene (HCB)
   and iron treatment. HCB was administered i.p. (totalling 300 mg/kg)
   twice, with 1 week interval. Three days after the first HCB injection
   iron-dextran was given i.p. (500 mg Fe per kg). Vitamin E was
   administered weekly (20 mg/kg) by s.c. injection. Both total hepatic
   porphyrin and LOOH levels were significantly (P<0.001) increased in
   the HCB-iron treated group as compared with the control group. Mice
   treated additionally with vitamin E had significant (P<0.001) lower
   levels as compared with the HCB-iron group. Similarly, the levels of
   8-OHdG were significantly (P<0.001) increased above controls after
   HCB-iron treatment and this increase was reduced after co-treatment
   with vitamin E (P<0.02). The data support the hypothesis that the
   mechanism of hepatic porphyrinogenicity of HCB with iron overload is
   an oxidative free radical process.
   
   PMID: 11397561, UI: 21291460
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