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Molecular insights into the pathogenesis of hereditary haemochromatosis
  1. A Pietrangelo
  1. Correspondence to:
    Professor A Pietrangelo
    Centre for Haemochromatosis and Hereditary Liver Diseases, Department of Internal Medicine, University of Modena and Reggio Emilia, Policlinico, Via del Pozzo 71, 41100 Modena Italy; pietrangelo.antonello{at}unimore.it

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In the past few years not many fields in medicine have been so profoundly transformed by seminal discoveries as the iron field. Key missing proteins in iron homeostasis have been characterised and their regulatory pathways or function dissected. Seemingly, the causative genes of the most important human diseases associated with deregulated iron metabolism and responsible for tissue iron overload have been identified. These giant steps forward have dramatically transformed the way we look at iron related diseases, their pathogenesis, diagnosis, and treatment. One of the best examples is the disorder known as haemochromatosis (HC) or hereditary haemochromatosis. This term was introduced to define the association of widespread tissue injury with massive tissue iron deposition1 and likely referred to a clinical entity named “bronze diabetes”2 and “cirrhose pigmentaire”3 first reported in France in the second half of the 19th century. After only one century the term was associated with an hereditary disease4 and linked to the major histocompatibility class I complex A3, on the short arm of chromosome 6.5,6 In 1996, the most prevalent HC gene, HFE, was cloned.7 However, once the HFE gene was identified, it appeared immediately clear that HFE mutations accounted for most but not all cases of HC.8 Since then, unprecedented progress in the field of iron genetics has led to the identification of new genes involved in iron metabolism whose mutations are responsible for cases of hereditary iron storage disorders.

The term haemochromatosis (HC) (synonymous for hereditary or idiopathic or primary haemochromatosis) defines an autosomal recessive disorder of iron metabolism characterised by tissue iron overload potentially leading to multiorgan disease, such as liver cirrhosis, endocrinopathy, and cardiomyopathy. The syndrome is the result of a genetically determined failure to stop iron from entering the circulatory pool when it …

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