The porphyrias: advances in diagnosis and treatment

Hematology Am Soc Hematol Educ Program. 2012:2012:19-27. doi: 10.1182/asheducation-2012.1.19.


The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as "acute hepatic," "hepatic cutaneous," and "erythropoietic cutaneous" diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic prophyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 5-Aminolevulinate Synthetase / metabolism
  • DNA / metabolism
  • Erythrocytes / cytology
  • Genes, Recessive
  • Genetic Therapy / methods
  • Hematology / methods
  • Hematology / trends
  • Heme / metabolism
  • Homozygote
  • Humans
  • Metabolism, Inborn Errors
  • Models, Biological
  • Mutation
  • Phlebotomy
  • Porphyria Cutanea Tarda / diagnosis
  • Porphyria Cutanea Tarda / genetics
  • Porphyria, Erythropoietic / diagnosis
  • Porphyria, Erythropoietic / genetics
  • Porphyrias / diagnosis*
  • Porphyrias / genetics
  • Porphyrias / therapy*
  • Skin / pathology
  • Stem Cells / cytology


  • Heme
  • DNA
  • 5-Aminolevulinate Synthetase
  • ALAS2 protein, human