Download PDF
Semin Liver Dis 2007; 27(1): 099-108
DOI: 10.1055/s-2006-960173
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Genetic Aspects of Porphyria Cutanea Tarda

Richard W. Lambrecht1 , Manish Thapar2 , Herbert L. Bonkovsky3
  • 1Department of Pharmacology, and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, Connecticut
  • 2Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut
  • 3Departments of Medicine and Molecular, Microbial, & Structural Biology, and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, Connecticut
Further Information

Publication History

Publication Date:
12 February 2007 (online)

    Permissions and Reprints

ABSTRACT

Porphyria cutanea tarda (PCT) is caused by disruption of heme biosynthesis at the step catalyzed by uroporphyrinogen decarboxylase. The patients present with photosensitive cutaneous lesions, hepatic pathology (including elevated porphyrin levels), and increased excretion of porphyrins. Therapy consists of removing the exacerbating factors of PCT (reduced sunlight exposure, abstinence from alcohol use, decreased estrogen exposure, and treatment for viral infections), decreasing body iron stores (by therapeutic phlebotomy or by the use of the new orally active iron chelators), and, in some instances, the use of low-dose antimalarials. Recent advances in genetics and genomics have allowed DNA testing for porphyria cutanea tarda and are likely to be instrumental in developing improved, gene-based treatments and in finding genetic loci (in addition to uroporphyrinogen decarboxylase) involved in the clinical expression of this disease.

KEYWORDS

Porphyria cutanea tarda - heme biosynthesis - genetics - genomics

REFERENCES

  • 1 Waldenstrom J. Studien ueber Porphyrie.  Acta Med Scand. 1937;  82(suppl) 1-254
    PubMedGoogle Scholar
  • 2 Elder G H. Porphyria cutanea tarda.  Semin Liver Dis. 1998;  18 67-75
    PubMedGoogle Scholar
  • 3 Sweeney G D. Porphyria cutanea tarda, or the uroporphyrinogen decarboxylase deficiency diseases.  Clin Biochem. 1986;  19 3-15
    PubMedGoogle Scholar
  • 4 Moran M J, Fontanellas A, Brudieux E et al.. Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: the influence of virus C infection.  Hepatology. 1998;  27 584-589
    CrossrefPubMedGoogle Scholar
  • 5 Elder G H. The cutaneous porphyrias.  Semin Dermatol. 1990;  9 63-69
    PubMedGoogle Scholar
  • 6 O'Reilly F M, Darby C, Fogarty J et al.. Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda.  Arch Dermatol. 1997;  133 1098-1101
    CrossrefPubMedGoogle Scholar
  • 7 Bonkovsky H L, Lambrecht R W, Shan Y. Iron as a co-morbid factor in nonhemochromatotic liver disease.  Alcohol. 2003;  30 137-144
    CrossrefPubMedGoogle Scholar
  • 8 Bonkovsky H L, Lambrecht R W. Iron-induced liver injury.  Clin Liver Dis. 2000;  4 409-429
    CrossrefPubMedGoogle Scholar
  • 9 Alla V, Bonkovsky H L. Iron in nonhemochromatotic liver disorders.  Semin Liver Dis. 2005;  25 461-472
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Felsher B F, Kushner J P. Hepatic siderosis and porphyria cutanea tarda: relation of iron excess to the metabolic defect.  Semin Hematol. 1977;  14 243-251
    PubMedGoogle Scholar
  • 11 Lambrecht R W, Jacobs J M, Sinclair P R, Sinclair J F. Inhibition of uroporphyrinogen decarboxylase activity: the role of cytochrome P-450-mediated uroporphyrinogen oxidation.  Biochem J. 1990;  269 437-441
    PubMedGoogle Scholar
  • 12 Lambrecht R W, Bonkovsky H L. Hemochromatosis and porphyria.  Semin Gastrointest Dis. 2002;  13 109-119
    PubMedGoogle Scholar
  • 13 Mukerji S K. Haem biosynthesis and human porphyria cutanea tarda: effects of alcohol intake.  Indian J Exp Biol. 2000;  38 635-642
    PubMedGoogle Scholar
  • 14 Daniell W E, Stockbridge H L, Labbe R F et al.. Environmental chemical exposures and disturbances of heme synthesis.  Environ Health Perspect. 1997;  105(suppl 1) 37-53
    PubMedGoogle Scholar
  • 15 Mor Z, Caspi E. Cutaneous complications of hormonal replacement therapy.  Clin Dermatol. 1997;  15 147-154
    PubMedGoogle Scholar
  • 16 Sterling R K, Bralow S. Extrahepatic manifestations of hepatitis C virus.  Curr Gastroenterol Rep. 2006;  8 53-59
    PubMedGoogle Scholar
  • 17 Almehmi A, Deliri H, Szego G G et al.. Porphyria cutanea tarda in a patient with HIV-infection.  W V Med J. 2005;  101 19-21
    PubMedGoogle Scholar
  • 18 Bonkovsky H L, Poh-Fitzpatrick M, Pimstone N et al.. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America.  Hepatology. 1998;  27 1661-1669
    CrossrefPubMedGoogle Scholar
  • 19 Kondo M, Yano Y, Shirataka M, Urata G, Sassa S. Porphyrias in Japan: compilation of all cases reported through 2002.  Int J Hematol. 2004;  79 448-456
    PubMedGoogle Scholar
  • 20 Badminton M N, Elder G H. Molecular mechanisms of dominant expression in porphyria.  J Inherit Metab Dis. 2005;  28 277-286
    CrossrefPubMedGoogle Scholar
  • 21 Elder G H, Urquhart A J, De Salamanca R E, Munoz J J, Bonkovsky H L. Immunoreactive uroporphyrinogen decarboxylase in the liver in porphyria cutanea tarda.  Lancet. 1985;  2 229-233
    PubMedGoogle Scholar
  • 22 Egger N G, Goeger D E, Payne D A et al.. Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency.  Dig Dis Sci. 2002;  47 419-426
    PubMedGoogle Scholar
  • 23 Armstrong D K, Sharpe P C, Chambers C R et al.. Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is associated with mild disease and an unusual porphyrin excretion pattern.  Br J Dermatol. 2004;  151 920-923
    CrossrefPubMedGoogle Scholar
  • 24 Elder G H, Smith S G, Herrero C et al.. Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase defect or homozygous porphyria cutanea tarda?.  Lancet. 1981;  1 916-919
    PubMedGoogle Scholar
  • 25 Cruz-Rojo J, Fontanellas A, Moran-Jimenez M J et al.. Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients.  Cell Mol Biol (Noisy-le-grand). 2002;  48 845-852
    PubMedGoogle Scholar
  • 26 Pimstone N R. Hematologic and hepatic manifestations of the cutaneous porphyrias.  Clin Dermatol. 1985;  3 83-102
    PubMedGoogle Scholar
  • 27 Bonkovsky H L. Mechanism of iron potentiation of hepatic uroporphyria: studies in cultured chick embryo liver cells.  Hepatology. 1989;  10 354-364
    PubMedGoogle Scholar
  • 28 Fracanzani A L, Taioli E, Sampietro M et al.. Liver cancer risk is increased in patients with porphyria cutanea tarda in comparison to matched control patients with chronic liver disease.  J Hepatol. 2001;  35 498-503
    CrossrefPubMedGoogle Scholar
  • 29 Shehan J M, Huerter C J. Porphyria cutanea tarda associated with an acute gastrointestinal bleed: the roles of supplemental iron and blood transfusion.  Cutis. 2001;  68 147-150
    PubMedGoogle Scholar
  • 30 Chemmanur A T, Bonkovsky H L. Hepatic porphyrias: diagnosis and management.  Clin Liver Dis. 2004;  8 807-838
    CrossrefPubMedGoogle Scholar
  • 31 Badiu C, Cristofor D, Voicu D, Coculescu M. Diagnostic traps in porphyria: case report and literature review.  Rev Med Chir Soc Med Nat Iasi. 2004;  108 584-591
    PubMedGoogle Scholar
  • 32 Lockwood W H, Poulos V, Rossi E, Curnow D H. Rapid procedure for fecal porphyrin assay.  Clin Chem. 1985;  31 1163-1167
    PubMedGoogle Scholar
  • 33 Cooper C L, Stob C M, Jones M A, Lash T D. Metabolism of pentacarboxylate porphyrinogens by highly purified human coproporphyrinogen oxidase: further evidence for the existence of an abnormal pathway for heme biosynthesis.  Bioorg Med Chem. 2005;  13 6244-6251
    CrossrefPubMedGoogle Scholar
  • 34 Lim C K, Peters T J. Urine and faecal porphyrin profiles by reversed-phase high-performance liquid chromatography in the porphyrias.  Clin Chim Acta. 1984;  139 55-63
    CrossrefPubMedGoogle Scholar
  • 35 Kostler E, Wollina U. Therapy of porphyria cutanea tarda.  Expert Opin Pharmacother. 2005;  6 377-383
    CrossrefPubMedGoogle Scholar
  • 36 Freesemann A, Frank M, Sieg I, Doss M O. Treatment of porphyria cutanea tarda by the effect of chloroquine on the liver.  Skin Pharmacol. 1995;  8 156-161
    PubMedGoogle Scholar
  • 37 Drago F, Battifoglio M L, Gelati G, Rebora A. Very low-dose chloroquine treatment for porphyria cutanea tarda.  Acta Derm Venereol. 1995;  75 329-330
    PubMedGoogle Scholar
  • 38 Berk D R, Mallory S B, Keeffe E B, Ahmed A. Dermatologic disorders associated with chronic hepatitis C: effect of interferon therapy.  Clin Gastroenterol Hepatol. 2006;  , August 16 (Epub ahead of print)
    PubMedGoogle Scholar
  • 39 Hift R J, Corrigall A V, Hancock V et al.. 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;  48 853-859
    PubMedGoogle Scholar
  • 40 Ajioka R S, Phillips J D, Kushner J P. Biosynthesis of heme in mammals.  Biochim Biophys Acta. 2006;  1763 723-736
    PubMedGoogle Scholar
  • 41 Ponka P. Cell biology of heme.  Am J Med Sci. 1999;  318 241-256
    CrossrefPubMedGoogle Scholar
  • 42 Tsiftsoglou A S, Tsamadou A I, Papadopoulou L C. Heme as key regulator of major mammalian cellular functions: molecular, cellular, and pharmacological aspects.  Pharmacol Ther. 2006;  111 327-345
    CrossrefPubMedGoogle Scholar
  • 43 Ibraham N G, Friedland M L, Levere R D. Heme metabolism in erythroid and hepatic cells.  Prog Hematol. 1983;  13 75-130
    PubMedGoogle Scholar
  • 44 Taketani S. Acquisition, mobilization and utilization of cellular iron and heme: endless findings and growing evidence of tight regulation.  Tohoku J Exp Med. 2005;  205 297-318
    CrossrefPubMedGoogle Scholar
  • 45 Podvinec M, Handschin C, Looser R, Meyer U A. Identification of the xenosensors regulating human 5-aminolevulinate synthase.  Proc Natl Acad Sci USA. 2004;  101 9127-9132
    CrossrefPubMedGoogle Scholar
  • 46 Surinya K H, Cox T C, May B K. Transcriptional regulation of the human erythroid 5-aminolevulinate synthase gene: identification of promoter elements and role of regulatory proteins.  J Biol Chem. 1997;  272 26585-26594
    CrossrefPubMedGoogle Scholar
  • 47 Munakata H, Sun J Y, Yoshida K et al.. Role of the heme regulatory motif in the heme-mediated inhibition of mitochondrial import of 5-aminolevulinate synthase.  J Biochem (Tokyo). 2004;  136 233-238
    CrossrefPubMedGoogle Scholar
  • 48 Cable E E, Gildemeister O S, Pepe J A et al.. Hepatic 5-aminolevulinic acid synthase mRNA stability is modulated by inhibitors of heme biosynthesis and by metalloporphyrins.  Eur J Biochem. 1996;  240 112-117
    CrossrefPubMedGoogle Scholar
  • 49 Kolluri S, Sadlon T J, May B K, Bonkovsky H L. Haem repression of the housekeeping 5-aminolaevulinic acid synthase gene in the hepatoma cell line LMH.  Biochem J. 2005;  392 173-180
    CrossrefPubMedGoogle Scholar
  • 50 Lincoln B C, Aw T Y, Bonkovsky H L. Heme catabolism in cultured hepatocytes: evidence that heme oxygenase is the predominant pathway and that a proportion of synthesized heme is converted rapidly to biliverdin.  Biochim Biophys Acta. 1989;  992 49-58
    PubMedGoogle Scholar
  • 51 Maines M D, Trakshel G M, Kutty R K. Characterization of two constitutive forms of rat liver microsomal heme oxygenase: only one molecular species of the enzyme is inducible.  J Biol Chem. 1986;  261 411-419
    PubMedGoogle Scholar
  • 52 Sun J, Hoshino H, Takaku K et al.. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene.  EMBO J. 2002;  21 5216-5224
    CrossrefPubMedGoogle Scholar
  • 53 Sun J, Brand M, Zenke Y et al.. Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network.  Proc Natl Acad Sci USA. 2004;  101 1461-1466
    CrossrefPubMedGoogle Scholar
  • 54 Shan Y, Lambrecht R W, Ghaziani T, Donohue S E, Bonkovsky H L. Role of Bach-1 in regulation of heme oxygenase-1 in human liver cells: insights from studies with small interfering RNAS.  J Biol Chem. 2004;  279 51769-51774
    CrossrefPubMedGoogle Scholar
  • 55 Shan Y, Lambrecht R W, Bonkovsky H L. Identification of key elements that are responsible for heme-mediated induction of the avian heme oxygenase-1 gene.  Biochim Biophys Acta. 2004;  1679 87-94
    PubMedGoogle Scholar
  • 56 Wijayanti N, Katz N, Immenschuh S. Biology of heme in health and disease.  Curr Med Chem. 2004;  11 981-986
    CrossrefPubMedGoogle Scholar
  • 57 Phillips J D, Jackson L K, Bunting M et al.. A mouse model of familial porphyria cutanea tarda.  Proc Natl Acad Sci USA. 2001;  98 259-264
    CrossrefPubMedGoogle Scholar
  • 58 Rao A U, Carta L K, Lesuisse E, Hamza I. Lack of heme synthesis in a free-living eukaryote.  Proc Natl Acad Sci USA. 2005;  102 4270-4275
    CrossrefPubMedGoogle Scholar
  • 59 Rothstein M, Coppens M. Nutritional factors and conditions for the axenic culture of free-living nematodes.  Comp Biochem Physiol B. 1978;  61 99-104
    PubMedGoogle Scholar
  • 60 Whitby F G, Phillips J D, Kushner J P, Hill C P. Crystal structure of human uroporphyrinogen decarboxylase.  EMBO J. 1998;  17 2463-2471
    CrossrefPubMedGoogle Scholar
  • 61 Martins B M, Grimm B, Mock H P, Huber R, Messerschmidt A. Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum: implications for the catalytic mechanism.  J Biol Chem. 2001;  276 44108-44116
    CrossrefPubMedGoogle Scholar
  • 62 Romana M, Le Boulch P, Romeo P H. Rat uroporphyrinogen decarboxylase cDNA: nucleotide sequence and comparison to human uroporphyrinogen decarboxylase.  Nucleic Acids Res. 1987;  15 7211
    CrossrefPubMedGoogle Scholar
  • 63 Phillips J D, Parker T L, Schubert H L et al.. Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase.  Blood. 2001;  98 3179-3185
    CrossrefPubMedGoogle Scholar
  • 64 Smith A G, Francis J E. Investigations of rat liver uroporphyrinogen decarboxylase: comparisons of porphyrinogens I and III as substrates and the inhibition by porphyrins.  Biochem J. 1981;  195 241-250
    PubMedGoogle Scholar
  • 65 Sinclair P, Lambrecht R, Sinclair J. Evidence for cytochrome P450-mediated oxidation of uroporphyrinogen by cell-free liver extracts from chick embryos treated with 3-methylcholanthrene.  Biochem Biophys Res Commun. 1987;  146 1324-1329
    CrossrefPubMedGoogle Scholar
  • 66 Jacobs J M, Sinclair P R, Bement W J et al.. Oxidation of uroporphyrinogen by methylcholanthrene-induced cytochrome P-450: essential role of cytochrome P-450d.  Biochem J. 1989;  258 247-253
    PubMedGoogle Scholar
  • 67 Jacobs J M, Sinclair P R, Lambrecht R W, Sinclair J F, Jacobs N J. Role of inducer binding in cytochrome P-450 IA2-mediated uroporphyrinogen oxidation.  J Biochem Toxicol. 1990;  5 193-199
    CrossrefPubMedGoogle Scholar
  • 68 Romana M, Dubart A, Beaupain D et al.. Structure of the gene for human uroporphyrinogen decarboxylase.  Nucleic Acids Res. 1987;  15 7343-7356
    CrossrefPubMedGoogle Scholar
  • 69 Hansen J L, Pryor M A, Kennedy J B, Kushner J P. Steady-state levels of uroporphyrinogen decarboxylase mRNA in lymphoblastoid cell lines from patients with familial porphyria cutanea tarda and their relatives.  Am J Hum Genet. 1988;  42 847-853
    PubMedGoogle Scholar
  • 70 Harraway J R, Florkowski C M, Sies C, George P M. Dual porphyria with mutations in both the UROD and HMBS genes.  Ann Clin Biochem. 2006;  43 80-82
    CrossrefPubMedGoogle Scholar
  • 71 Christiansen L, Brons-Poulsen J, Horder M, Brock A, Petersen N E. Expression and characterization of six clinically relevant uroporphyrinogen decarboxylase gene mutations.  Scand J Clin Lab Invest. 2005;  65 227-235
    PubMedGoogle Scholar
  • 72 Mendez M, Rossetti M V, Del C Batlle A M, Parera V E. The role of inherited and acquired factors in the development of porphyria cutanea tarda in the Argentinean population.  J Am Acad Dermatol. 2005;  52 417-424
    CrossrefPubMedGoogle Scholar
  • 73 Poblete-Gutierrez P, Mendez M, Wiederholt T et al.. The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene.  Exp Dermatol. 2004;  13 372-379
    CrossrefPubMedGoogle Scholar
  • 74 Martinez di Montemuros F, Tavazzi D, Patti E, Cappellini M D. Human gene mutations. Gene symbol: UROD. Disease: porphyria, cutanea tarda.  Hum Genet. 2004;  114 221
    PubMedGoogle Scholar
  • 75 Martinez di Montemuros F, Tavazzi D, Patti E, Cappellini M D. Gene symbol: UROD. Disease: porphyria, cutanea tarda.  Hum Genet. 2003;  113 368
    PubMedGoogle Scholar
  • 76 Martinez di Montemuros F, Di Pierro E, Patti E et al.. Molecular characterization of porphyrias in Italy: a diagnostic flow-chart.  Cell Mol Biol (Noisy-le-grand). 2002;  48 867-876
    PubMedGoogle Scholar
  • 77 Ged C, Ozalla D, Herrero C et al.. Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus.  Arch Dermatol. 2002;  138 957-960
    CrossrefPubMedGoogle Scholar
  • 78 Cappellini M D, Martinez di Montemuros F, Tavazzi D et al.. Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT).  Hum Mutat. 2001;  17 350
    PubMedGoogle Scholar
  • 79 Christiansen L, Ged C, Hombrados I et al.. Screening for mutations in the uroporphyrinogen decarboxylase gene using denaturing gradient gel electrophoresis: identification and characterization of six novel mutations associated with familial PCT.  Hum Mutat. 1999;  14 222-232
    CrossrefPubMedGoogle Scholar
  • 80 McManus J F, Begley C G, Sassa S, Ratnaike S. Three new mutations in the uroporphyrinogen decarboxylase gene in familial porphyria cutanea tarda: mutation in brief no. 237. Online.  Hum Mutat. 1999;  13 412
    PubMedGoogle Scholar
  • 81 McManus J F, Begley C G, Sassa S, Ratnaike S. Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria.  Blood. 1996;  88 3589-3600
    PubMedGoogle Scholar
  • 82 Garey J R, Hansen J L, Harrison L M, Kennedy J B, Kushner J P. A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda.  Blood. 1989;  73 892-895
    PubMedGoogle Scholar
  • 83 Garey J R, Harrison L M, Franklin K F et al.. Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda.  J Clin Invest. 1990;  86 1416-1422
    PubMedGoogle Scholar
  • 84 Peters H A, Cripps D J, Lambrecht R W et al.. History and geography of hexachlorobenzene poisoning in southeastern Turkey.  IARC Sci Publ. 1986;  (77) 131-132
    PubMedGoogle Scholar
  • 85 Erturk E, Lambrecht R W, Peters H A et al.. Oncogenicity of hexachlorobenzene.  IARC Sci Publ. 1986;  (77) 417-423
    PubMedGoogle Scholar
  • 86 Lambrecht R W, Sinclair P R, Bement W J, Sinclair J F. Uroporphyrin accumulation in cultured chick embryo hepatocytes: comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,4,3′,4′-tetrachlorobiphenyl.  Toxicol Appl Pharmacol. 1988;  96 507-516
    CrossrefPubMedGoogle Scholar
  • 87 Gorman N, Ross K L, Walton H S et al.. Uroporphyria in mice: thresholds for hepatic CYP1A2 and iron.  Hepatology. 2002;  35 912-921
    CrossrefPubMedGoogle Scholar
  • 88 Lambrecht R W, Sinclair P R, Bement W J et al.. Hepatic uroporphyrin accumulation and uroporphyrinogen decarboxylase activity in cultured chick-embryo hepatocytes and in Japanese quail (Coturnix coturnix japonica) and mice treated with polyhalogenated aromatic compounds.  Biochem J. 1988;  253 131-138
    PubMedGoogle Scholar
  • 89 Cantoni L, Graziani A, Rizzardini M, Saletti M C. Porphyrinogenic effect of hexachlorobenzene and 2,3,7,8-tetrachlorodibenzo-para-dioxin: is an inhibitor involved in uroporphyrinogen decarboxylase inactivation?.  IARC Sci Publ. 1986;  (77) 449-456
    PubMedGoogle Scholar
  • 90 Goldstein J A, Friesen M, Scotti T M et al.. Assessment of the contribution of chlorinated dibenzo-p-dioxins and dibenzofurans to hexachlorobenzene-induced toxicity, porphyria, changes in mixed function oxygenases, and histopathological changes.  Toxicol Appl Pharmacol. 1978;  46 633-649
    CrossrefPubMedGoogle Scholar
  • 91 Bowers M A, Luckhurst C L, Davis H A, Woods J S. Investigation of factors influencing urinary porphyrin excretion in rats: strain, gender, and age.  Fundam Appl Toxicol. 1992;  19 538-544
    CrossrefPubMedGoogle Scholar
  • 92 Wang H, Long Q, Marty S D, Sassa S, Lin S. A zebrafish model for hepatoerythropoietic porphyria.  Nat Genet. 1998;  20 239-243
    PubMedGoogle Scholar
  • 93 Cappellini M D. Iron-chelating therapy with the new oral agent ICL670 (Exjade).  Best Pract Res Clin Haematol. 2005;  18 289-298
    CrossrefPubMedGoogle Scholar
  • 94 Vanorden H E, Hagemann T M. Deferasirox: an oral agent for chronic iron overload.  Ann Pharmacother. 2006;  40 1110-1117
    PubMedGoogle Scholar
  • 95 Fontanellas A, Mazurier F, Moreau-Gaudry F et al.. Correction of uroporphyrinogen decarboxylase deficiency (hepatoerythropoietic porphyria) in Epstein-Barr virus-transformed B-cell lines by retrovirus-mediated gene transfer: fluorescence-based selection of transduced cells.  Blood. 1999;  94 465-474
    PubMedGoogle Scholar
  • 96 Richard E, Geronimi F, Lalanne M et al.. A bicistronic SIN-lentiviral vector containing G156A MGMT allows selection and metabolic correction of hematopoietic protoporphyric cell lines.  J Gene Med. 2003;  5 737-747
    CrossrefPubMedGoogle Scholar

Richard W LambrechtPh.D. 

Assistant Professor, Department of Pharmacology, and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center

263 Farmington Avenue, Farmington, CT 06030-1119