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Heme Synthesis Defects and Porphyrias

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

Abstract

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.

Keywords

Porphyria Cutanea Tarda Molecular Adsorbent Recirculation System Acute Intermittent Porphyria Acute Intermittent Porphyria Acute Porphyria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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