Book contents
- Frontmatter
- Contents
- Foreword by Anthony S. Tavill
- Preface
- 1 History of iron overload disorders
- 2 Normal iron absorption and metabolism
- 3 Iron toxicity
- 4 Tests for hemochromatosis and iron overload
- 5 Complications of hemochromatosis and iron overload
- 6 Insulin resistance and iron overload
- 7 Infections and immunity
- 8 Classical and atypical HFE hemochromatosis
- 9 Heterozygosity for HFE C282Y
- 10 Porphyria cutanea tarda
- 11 Mitochondrial mutations as modifiers of hemochromatosis
- 12 Hemochromatosis associated with ferroportin gene (SLC40A1) mutations
- 13 Hemochromatosis associated with hemojuvelin gene (HJV) mutations
- 14 Hemochromatosis associated with hepcidin gene (HAMP) mutations
- 15 Hemochromatosis associated with transferrin receptor-2 gene (TFR2) mutations
- 16 Iron overload associated with IRE mutation of ferritin heavy-chain gene (FTH1)
- 17 Hereditary hyperferritinemia-cataract syndrome: IRE mutations of ferritin light-chain gene (FTL)
- 18 Iron overload in Native Africans and African-Americans
- 19 Hereditary atransferrinemia
- 20 Divalent metal transporter-1 (SLC11A2) iron overload
- 21 Iron overload associated with thalassemia syndromes
- 22 Iron overload associated with hemoglobinopathies
- 23 Iron overload associated with pyruvate kinase deficiency
- 24 Iron overload associated with congenital dyserythropoietic anemias
- 25 Hereditary sideroblastic anemias
- 26 Pearson marrow–pancreas syndrome
- 27 Acquired sideroblastic anemias
- 28 Hereditary aceruloplasminemia
- 29 Friedreich ataxia and cardiomyopathy
- 30 Pantothenate kinase (PANK2)-associated neurodegeneration
- 31 Neuroferritinopathies
- 32 GRACILE syndrome
- 33 Neonatal hemochromatosis
- 34 Iron overload due to excessive supplementation
- 35 Localized iron overload
- 36 Management of iron overload
- 37 Population screening for hemochromatosis
- 38 Ethical, legal, and social implications
- 39 Directions for future research
- Index
- Plate section
- References
10 - Porphyria cutanea tarda
Published online by Cambridge University Press: 01 June 2011
Book contents
- Frontmatter
- Contents
- Foreword by Anthony S. Tavill
- Preface
- 1 History of iron overload disorders
- 2 Normal iron absorption and metabolism
- 3 Iron toxicity
- 4 Tests for hemochromatosis and iron overload
- 5 Complications of hemochromatosis and iron overload
- 6 Insulin resistance and iron overload
- 7 Infections and immunity
- 8 Classical and atypical HFE hemochromatosis
- 9 Heterozygosity for HFE C282Y
- 10 Porphyria cutanea tarda
- 11 Mitochondrial mutations as modifiers of hemochromatosis
- 12 Hemochromatosis associated with ferroportin gene (SLC40A1) mutations
- 13 Hemochromatosis associated with hemojuvelin gene (HJV) mutations
- 14 Hemochromatosis associated with hepcidin gene (HAMP) mutations
- 15 Hemochromatosis associated with transferrin receptor-2 gene (TFR2) mutations
- 16 Iron overload associated with IRE mutation of ferritin heavy-chain gene (FTH1)
- 17 Hereditary hyperferritinemia-cataract syndrome: IRE mutations of ferritin light-chain gene (FTL)
- 18 Iron overload in Native Africans and African-Americans
- 19 Hereditary atransferrinemia
- 20 Divalent metal transporter-1 (SLC11A2) iron overload
- 21 Iron overload associated with thalassemia syndromes
- 22 Iron overload associated with hemoglobinopathies
- 23 Iron overload associated with pyruvate kinase deficiency
- 24 Iron overload associated with congenital dyserythropoietic anemias
- 25 Hereditary sideroblastic anemias
- 26 Pearson marrow–pancreas syndrome
- 27 Acquired sideroblastic anemias
- 28 Hereditary aceruloplasminemia
- 29 Friedreich ataxia and cardiomyopathy
- 30 Pantothenate kinase (PANK2)-associated neurodegeneration
- 31 Neuroferritinopathies
- 32 GRACILE syndrome
- 33 Neonatal hemochromatosis
- 34 Iron overload due to excessive supplementation
- 35 Localized iron overload
- 36 Management of iron overload
- 37 Population screening for hemochromatosis
- 38 Ethical, legal, and social implications
- 39 Directions for future research
- Index
- Plate section
- References
Summary
Porphyrias are disorders caused by heritable or acquired deficiency of an enzyme that is required for the normal synthesis of heme. A ring structure, heme is formed by the insertion of an iron atom into protoporphyrin in the final step of the porphyrin synthesis pathway. The usual presenting symptoms and signs of porphyrias are either skin photosensitivity or neurovisceral symptoms and signs. Three types of porphyria are characterized by a predominance of photosensitivity (porphyria cutanea tarda (PCT), congenital erythropoietic porphyria, and erythropoietic protoporphyria). Two types of porphyria are characterized mainly by neurovisceral symptoms and signs (acute intermittent porphyria and aminolevulinate dehydratase deficiency). The two remaining types of porphyria are characterized by both photosensitivity and neurovisceral symptoms and signs (hereditary coproporphyria and variegate porphyria). The seven main types of porphyria, the associated enzyme deficiency, the mode of inheritance, and the major presenting symptoms and signs are displayed in Table 10.1. The only type of porphyria discussed here is PCT, the most common of all porphyrias.
Porphyria cutanea tarda (PCT)
PCT is estimated to occur in about 1 per 5000 to 25,000 individuals in the general population. PCT is caused by decreased specific activity of the uroporphyrinogen decarboxylase enzyme, the fifth enzyme in the heme synthesis pathway. Three types of PCT can be identified on the basis of decreased activity of the uroporphyrinogen decarboxylase enzyme (URO-D) in liver cells or in erythrocytes.
- Type
- Chapter
- Information
- Handbook of Iron Overload Disorders , pp. 160 - 168Publisher: Cambridge University PressPrint publication year: 2010
References
. Molecular genetics of disorders of haem biosynthesis. J Clin Pathol 1993; 46: 977–81.CrossRefGoogle ScholarPubMed
, , , , . A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda. Proc Natl Acad Sci USA 2007; 104: 5079–84.CrossRefGoogle ScholarPubMed
, , , et al. Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood 2000; 95: 15651.Google ScholarPubMed
, , . Genetic aspects of porphyria cutanea tarda. Semin Liver Dis 2007; 27: 99–108.CrossRefGoogle ScholarPubMed
, , , et al. Hemochromatosis (HFE) and transferrin receptor-1 (TFRC1) genes in sporadic porphyria cutanea tarda (sPCT). Cell Mol Biol (Noisy-le-grand) 2002; 48: 33–41.Google Scholar
, , , et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in north America. Hepatology 1998; 27: 1661–9.CrossRefGoogle ScholarPubMed
, , , et al. The C282Y mutation in the haemochromatosis gene (HFE) and hepatitis C virus infection are independent cofactors for porphyria cutanea tarda in Australian patients. J Hepatol 1998; 28: 404–9.CrossRefGoogle ScholarPubMed
, , , et al. Hepatitis C virus and porphyria cutanea tarda: evidence of a strong association. Hepatology 1992; 16: 1322–6.CrossRefGoogle ScholarPubMed
, , , et al. Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda. Arch Dermatol 2003; 139: 309–13.CrossRefGoogle ScholarPubMed
, , , , . Are His63Asp or Cys282Tyr HFE mutations associated with porphyria cutanea tarda? Data of patients from central and southern Italy. J Invest Dermatol 1998; 111: 1241–2.CrossRefGoogle ScholarPubMed
, , . Mutations of the hereditary hemochromatosis candidate gene HLA-H in porphyria cutanea tarda. N Engl J Med 1997; 336: 1327–8.CrossRefGoogle ScholarPubMed
, , , , . Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda. Lancet 1997; 349: 321–3.CrossRefGoogle ScholarPubMed
, , , , , The most frequent HFE allele linked to porphyria cutanea tarda in Mediterraneans is His63Asp. Hepatology 1999; 30: 819–20.CrossRefGoogle Scholar
, , , , . Extremely rare association of HFE mutations with porphyria cutanea tarda in Japanese patients. Hepatology 1999; 30: 1532–3.CrossRefGoogle ScholarPubMed
, , , , , . Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency. Dig Dis Sci 2002; 47: 419–26.CrossRefGoogle ScholarPubMed
, , , . Association of porphyria cutanea tarda with hereditary hemochromatosis. J Am Acad Dermatol 2004; 51: 205–11.CrossRefGoogle ScholarPubMed
, , , , , . Denaturing gradient gel electrophoresis analysis of the hemochromatosis (HFE) gene: impact of HFE gene mutations on the manifestation of porphyria cutanea tarda. Clin Chem 1999; 45: 2025–6.Google ScholarPubMed
, , , et al. Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda. J Invest Dermatol 2000; 115: 8684.CrossRefGoogle ScholarPubMed
, , , , , . The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection. J Eur Acad Dermatol Venereol 2006; 20: 1201–6.CrossRefGoogle ScholarPubMed
, , , et al. Human leukocyte antigen haplotypes and HFE mutations in Spanish hereditary hemochromatosis and sporadic porphyria cutanea tarda. J Gastroenterol Hepatol 2005; 20: 456–62.CrossRefGoogle ScholarPubMed
, , , , , Porphyria cutanea tarda, C282Y, H63D, and S65C HFE gene mutations and hepatitis C infection: a study from southern France. Dermatology 2003; 206: 212–16.CrossRefGoogle ScholarPubMed
, , , , , [Role of the hemochromatosis gene in prophyria cutanea tarda. Prospective study of 56 cases.]Ann Dermatol Venereol 2001; 128: 600–4.Google Scholar
, , , et al. HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France. Br J Dermatol 2001; 144: 533–9.CrossRefGoogle ScholarPubMed
, , , et al. High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda. Hepatology 1998; 27: 181–4.CrossRefGoogle ScholarPubMed
, , , , , Hemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda. Physiol Res 2006; 55 Suppl 2: S75–83.Google ScholarPubMed
, , , et al. C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients. Virchows Arch 2001; 439: 1.CrossRefGoogle ScholarPubMed
, , , et al. Hemochromatosis (HFE) gene mutations and hepatitis C virus infection as risk factors for porphyria cutanea tarda in Hungarian patients. Liver Int 2004; 24: 16–20.CrossRefGoogle ScholarPubMed
, , , , , [Significance and prevalence of the C282Y gene mutation of primary hemochromatosis in the pathogenesis of pophyria cutanea tarda.]Cas Lek Cesk 2000; 139: 728–30.Google Scholar
, , , , , . C282Y and H63D mutations in the HFE gene are not associated with porphyria cutanea tarda in Bulgaria. Hepatology 1999; 30: 1531–2.CrossRefGoogle Scholar
, , , [Mutations of hemochromatosis gene in volunteer blood donors and Chilean porphyria cutanea tarda patients.]Medicina (B Aires) 2006; 66: 421–6.Google Scholar
, , , . The role of inherited and acquired factors in the development of porphyria cutanea tarda in the Argentinean population. J Am Acad Dermatol 2005; 52: 417–24.CrossRefGoogle ScholarPubMed
, , , et al. Porphyria cutanea tarda in Brazilian patients: association with hemochromatosis C282Y mutation and hepatitis C virus infection. Am J Gastroenterol 2000; 95: 3516–21.CrossRefGoogle ScholarPubMed
, , , , , . Porphyria cutanea tarda: the etiological importance of mutations in the HFE gene and viral infection is population-dependent. Cell Mol Biol (Noisy-le-grand) 2002; 48: 853–9.Google ScholarPubMed
, , , et al. Transdermal estrogen replacement therapy in postmenopausal women previously treated for porphyria cutanea tarda. J Lab Clin Med 2000; 136: 482–8.CrossRefGoogle ScholarPubMed
, , , et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321–33.Google ScholarPubMed
, . Remission of porphyria cutanea tarda after anastrozole treatment of breast cancer. Clin Breast Cancer 2007; 7: 716–18.CrossRefGoogle ScholarPubMed
, , , , . A case of porphyria cutanea tarda resulting in digital amputation and improved by anastrazole. Clin Exp Dermatol 2007; 32: 327–8.CrossRefGoogle ScholarPubMed
, , , et al. The frequency of hemochromatosis-associated alleles is increased in British patients with sporadic porphyria cutanea tarda. Hepatology 1997; 25: 159–61.CrossRefGoogle ScholarPubMed