Abstract
Porphyrias are a group of inherited and acquired metabolic disorders due to a defect in haem biosynthesis. An enzymatic defect at different steps of haem synthesis leads to tissue accumulation and excessive excretion of porphyrins and/or their toxic precursors. The specific patterns of accumulation determine the variety of clinical manifestations, ranging from acute neurovisceral attacks to skin lesions and liver disease. Most enzyme defects represent partial deficiencies, while familial cases are linked to autosomal or recessive traits. The incomplete penetrance of the genetic defects often requires the triggering or aggravating effect of host-related or environmental factors. While genetics has a role in confirming clinical suspicion and in family screening, biochemical and clinical studies are still central in the diagnosis.
References
Puy H, Gouya L, Deybach JC (2010) Porphyrias. Lancet 375:924–937
Moore MR (1998) The biochemistry of heme synthesis in porphyria and in the porphyrinurias. Clin Dermatol 16:203–223
Fraser DJ, Podvinec M, Kaufmann MR, Meyer UA (2002) Drugs mediate the transcriptional activation of the 5-aminolevulinic acid synthase (ALAS1) gene via the chicken xenobiotic-sensing nuclear receptor (CXR). J Biol Chem 277:34717–34726
Smith SJ, Cox TM (1997) Translational control of erythroid delta-aminolevulinate synthase in immature human erythroid cells by heme. Cell Mol Biol (Noisy-le-grand) 43:103–114
Sassa S, Kappas A (2000) Molecular aspects of the inherited porphyrias. J Intern Med 247:169–178
Erskine PT, Norton E, Cooper JB et al (1999) X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution. Biochemistry 38:4266–4276
Sassa S (1998) ALAD porphyria. Semin Liver Dis 18:95–101
Ventura P, Cappellini MD, Rocchi E (2009) The acute porphyrias: a diagnostic and therapeutic challenge in internal and emergency medicine. Intern Emerg Med 4:297–308
Thunell S, Floderus Y, Henrichson A, Harper P (2006) Porphyria in Sweden. Physiol Res 55(Suppl 2):S109–S118
Chretien S, Dubart A, Beaupain D et al (1988) Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression. Proc Natl Acad Sci USA 85:6–10
Grandchamp B, Puy H, Lamoril J, Deybach JC, Nordmann Y (1996) Review: molecular pathogenesis of hepatic acute porphyrias. J Gastroenterol Hepatol 11:1046–1052
Martinez di Montemuros F, Di Pierro E, Biolcati G et al (2001) Acute intermittent porphyria: heterogeneity of mutations in the hydroxymethylbilane synthase gene in Italy. Blood Cells Mol Dis 27:961–970
Brownlie PD, Lambert R, Louie GV et al (1994) The three-dimensional structures of mutants of porphobilinogen deaminase: toward an understanding of the structural basis of acute intermittent porphyria. Protein Sci 3:1644–1650
Ged C, Moreau-Gaudry F, Richard E, Robert-Richard E, de Verneuil H (2009) Congenital erythropoietic porphyria: mutation update and correlations between genotype and phenotype. Cell Mol Biol (Noisy-le-grand) 55:53–60
Desnick RJ, Glass IA, Xu W, Solis C, Astrin KH (1998) Molecular genetics of congenital erythropoietic porphyria. Semin Liver Dis 18:77–84
Elder GH (1998) Porphyria cutanea tarda. Semin Liver Dis 18:67–75
Fargion S, Fracanzani AL (2003) Prevalence of hepatitis C virus infection in porphyria cutanea tarda. J Hepatol 39:635–638
Rocchi E, Gibertini P, Cassanelli M et al (1986) Hepatitis B virus infection in porphyria cutanea tarda. Liver 6:153–157
Cappellini MD, Martinez di Montemuros F, Tavazzi D et al (2001) Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT). Hum Mutat 17:350
Fargion S, Fracanzani AL, Romano R et al (1996) Genetic hemochromatosis in Italian patients with porphyria cutanea tarda: possible explanation for iron overload. J Hepatol 24:564–569
Takahashi S, Taketani S, Akasaka JE et al (1998) Differential regulation of coproporphyrinogen oxidase gene between erythroid and nonerythroid cells. Blood 92:3436–3444
Rocchi E, Pietrangelo A, Gibertini P et al (1984) Hereditary coproporphyria. A familial study. Recenti Prog Med 75:123–131
Lee DS, Flachsova E, Bodnarova M et al (2005) Structural basis of hereditary coproporphyria. Proc Natl Acad Sci USA 102:14232–14237
Di Pierro E, Ventura P, Brancaleoni V et al (2009) Clinical, biochemical and genetic characteristics of variegate porphyria in Italy. Cell Mol Biol (Noisy-le-grand) 55:79–88
Hift RJ, Meissner PN, Corrigall AV et al (1997) Variegate porphyria in South Africa, 1688–1996––new developments in an old disease. S Afr Med J 87:722–731
Meissner PN, Dailey TA, Hift RJ et al (1996) A R59 W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. Nat Genet 13:95–97
Rufenacht UB, Gouya L, Schneider-Yin X et al (1998) Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet 62:1341–1352
Martinez di Montemuros F, Di Pierro E, Patti E et al (2002) Molecular characterization of porphyrias in Italy: a diagnostic flow-chart. Cell Mol Biol (Noisy-le-grand) 48:867–876
Schneider-Yin X, Rufenacht UB, Hergersberg M et al (2001) Haplotype analysis in determination of the heredity of erythropoietic protoporphyria among Swiss families. J Invest Dermatol 117:1521–1525
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This article was retracted due to plagiarism.
An erratum to this article can be found at http://dx.doi.org/10.1007/s11739-011-0571-1
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Pietrangelo, A. RETRACTED ARTICLE: The porphyrias: pathophysiology. Intern Emerg Med 5 (Suppl 1), 65–71 (2010). https://doi.org/10.1007/s11739-010-0452-z
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DOI: https://doi.org/10.1007/s11739-010-0452-z