Heme Synthesis Defects and Porphyrias

  • Ulrich StölzelEmail author
  • Thomas Stauch
  • Manfred O. Doss


Porphyrias are metabolic disorders of the heme biosynthesis. Clinically, they can be differentiated into acute and non-acute porphyrias. The symptomatic phase of acute hepatic porphyrias is characterized by overproduction of neurotoxic porphyrin precursors and porphyrins. Acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and Doss porphyria (ALSDP) belong to this group of metabolic disorders. The clinical presentation of the acute hepatic porphyria syndrome includes abdominal, psychiatric, neurological, and cardiovascular symptoms. The diagnosis is based on an at least tenfold increased urinary excretion of porphobilinogen (apart from Doss porphyria and lead intoxication). Besides symptomatic therapy with non-porphyrinogenic drugs, electrolyte compensation, and intensive monitoring, intravenous administration of glucose and heme arginate is established for treatment. Among the non-acute types like porphyria cutanea tarda, erythropoietic protoporphyria, and congenital erythropoietic porphyria, the accumulated porphyrins cause photosensitivity of the skin and in some cases severe liver damage. X-linked protoporphyria (XLPP) represents a new type of protoporphyria, with 5-aminolevulinic acid synthase 2 gain of function leading to high concentrations of free protoporphyrin IX. The location of the deficient enzyme within the heme biosynthetic pathway determines the pattern of the accumulated porphyrins. The cDNA of all enzymes of heme biosynthesis have been characterized, and mutations responsible for any of the porphyrias have been described. Besides light protection, there are different therapies depending on the type of non-acute porphyria. Ultimately, liver transplantation may be considered in therapy-resistant cases of acute hepatic porphyrias and bone marrow transplantation in severe cases of erythropoietic porphyrias.


Porphyria Cutanea Tarda Molecular Adsorbent Recirculation System Acute Intermittent Porphyria Acute Intermittent Porphyria Acute Porphyria 
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  1. Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, Desnick RJ (2005) Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 142:439–450PubMedCrossRefGoogle Scholar
  2. Bonkovsky HL (1993) Advances in understanding and treating ‘the little imitator’, acute porphyria. Gastroenterology 105:590–594PubMedGoogle Scholar
  3. Bonkovsky HL, Guo JT, Hou W, Li T, Narang T, Thapar M (2013) Porphyrin and heme metabolism and the porphyrias. Compr Physiol 3:365–401PubMedGoogle Scholar
  4. Bonkowsky HL, Tschudy DP, Collins A, Doherty J, Bossenmaier I, Cardinal R, Watson CJ (1971) Repression of the overproduction of porphyrin precursors in acute intermittent porphyria by intravenous infusions of hematin. Proc Natl Acad Sci U S A 68:2725–2729PubMedCentralPubMedCrossRefGoogle Scholar
  5. Doss M, Verspohl F (1981) The “glucose effect” in acute hepatic porphyrias and in experimental porphyria. Klin Wochenschr 59:727–735PubMedCrossRefGoogle Scholar
  6. Doss M, von Tiepermann R, Schneider J, Schmid H (1979) New type of hepatic porphyria with porphobilinogen synthase defect and intermittent acute clinical manifestation. Klin Wochenschr 57:1123–1127PubMedCrossRefGoogle Scholar
  7. Handschin C, Lin J, Rhee J, Peyer AK, Chin S, Wu PH, Meyer UA, Spiegelman BM (2005) Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha. Cell 122:505–515PubMedCrossRefGoogle Scholar
  8. Kostler E, Wollina U (2005) Therapy of porphyria cutanea tarda. Expert Opin Pharmacother 6:377–383PubMedCrossRefGoogle Scholar
  9. Kühnel A, Groß U, Doss MO (2002) Porphyrien. In: Schmailzl KJG, Hachelöer BJ (eds) Schwangerschaft und Krankheit. Blackwell Verlag, Berlin/Wien, pp S440–S453Google Scholar
  10. Puy H, Gouya L, Deybach JC (2010) Porphyrias. Lancet 375:924–937PubMedCrossRefGoogle Scholar
  11. Seth AK, Badminton MN, Mirza D, Russell S, Elias E (2007) Liver transplantation for porphyria: who, when, and how? Liver Transpl 13:1219–1227PubMedCrossRefGoogle Scholar
  12. Stölzel U, Doss M (2009) Porphyrias. In: Dancygier H (ed) Clinical hepatology, principles and practice of hepatobiliary diseases, vol 2. Springer, Berlin, pp 1077–1092Google Scholar
  13. Stölzel U, Doss MO, Dissmann T, Cervós-Navarro J, Riecken EO (1987) Gastroenterologic and neurologic manifestations in acute intermittent porphyria. Med Klin (Munich) 82:520–525Google Scholar
  14. Stölzel U, Köstler E, Koszka C, Stöffler-Meilicke M, Schuppan D, Somasundaram R, Doss MO, Habermehl KO, Riecken EO (1995) Low prevalence of hepatitis C virus infection in porphyria cutanea tarda in Germany. Hepatology 21:1500–1503PubMedGoogle Scholar
  15. Stölzel U, Köstler E, Schuppan D, Richter M, Wollina U, Doss MO, Wittekind C, Tannapfel A (2003) Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda. Arch Dermatol 139:309–313PubMedCrossRefGoogle Scholar
  16. Stölzel U, Brosche C, Koszka C, Stauch T, Teubner A, Doss MO (2009) Safe and probably safe drugs in acute porphyria. Cell Mol Biol 55:147–151PubMedGoogle Scholar
  17. Wahlin S, Aschan J, Björnstedt M, Broomé U, Harper P (2007) Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis. J Hepatol 46:174–179PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ulrich Stölzel
    • 1
    Email author
  • Thomas Stauch
    • 2
  • Manfred O. Doss
    • 3
  1. 1.Department of Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, Metabolic Disorders, OncologySaxony Porphyria Center, Klinikum Chemnitz gGmbHChemnitzGermany
  2. 2.Department of Clinical Chemistry and ToxicologyGerman Competence Center for Porphyria Diagnosis and Consultation, MVZ Labor PD Dr. Volkmann und Kollegen GbRKarlsruheGermany
  3. 3.German Competence Center for Porphyria Diagnosis and ConsultationMarburg an der LahnGermany

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