Haemochromatosis

Lancet. 2016 Aug 13;388(10045):706-16. doi: 10.1016/S0140-6736(15)01315-X. Epub 2016 Mar 12.

Abstract

Haemochromatosis is now known to be an iron-storage disease with genetic heterogeneity but with a final common metabolic pathway resulting in inappropriately low production of the hormone hepcidin. This leads to increase in intestinal absorption and deposition of excessive amounts of iron in parenchymal cells which in turn results in eventual tissue damage and organ failure. A clinical enigma has been the variable clinical expression with some patients presenting with hepatic cirrhosis at a young age and others almost asymptomatic for life. Research is unravelling this puzzle by identifying environmental factors-especially alcohol consumption-and associated modifying genes that modulate phenotypic expression. A high index of suspicion is required for early diagnosis but this can lead to presymptomatic therapy and a normal life expectancy. Venesection (phlebotomy) therapy remains the mainstay of therapy, but alternative therapies are the subject of current research.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Cation Transport Proteins / genetics
  • Disease Management
  • Environmental Exposure
  • Europe / epidemiology
  • European Continental Ancestry Group / genetics
  • Ferritins / blood
  • Genetic Testing*
  • Genotype
  • Hemochromatosis Protein
  • Hemochromatosis* / diagnosis
  • Hemochromatosis* / genetics
  • Hemochromatosis* / physiopathology
  • Hemochromatosis* / therapy
  • Hepcidins / deficiency*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Iron / metabolism*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver Diseases / etiology
  • Liver Diseases / physiopathology
  • Liver Diseases / therapy
  • Mass Screening / methods
  • Mass Screening / standards
  • Membrane Proteins / genetics
  • Mutation*
  • Phenotype
  • Phlebotomy*
  • Polymorphism, Single Nucleotide
  • Receptors, Transferrin / genetics
  • Risk Factors
  • Sex Factors
  • Uncertainty

Substances

  • Cation Transport Proteins
  • HFE protein, human
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Receptors, Transferrin
  • TFR2 protein, human
  • metal transporting protein 1
  • Ferritins
  • Iron