Semin Liver Dis 2005; 25(4): 411-419
DOI: 10.1055/s-2005-923313
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pathophysiology of Hereditary Hemochromatosis

Robert E. Fleming1 , 2 , Robert S. Britton3 , Abdul Waheed2 , William S. Sly2 , Bruce R. Bacon3
  • 1Associate Professor, Department of Pediatrics, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri
  • 2Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri
  • 3Division of Gastroenterology and Hepatology, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri
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Publikationsdatum:
29. November 2005 (online)

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ABSTRACT

Hereditary hemochromatosis (HH) encompasses several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue iron deposition. The most common form of this disorder is HFE-related HH, nearly always caused by homozygosity for the C282Y mutation. A substantial proportion of C282Y homozygotes do not develop clinically significant iron overload, suggesting roles for environmental factors and modifier genes in determining the phenotype. Recent studies have demonstrated that the pathogenesis of nearly all forms of HH involves inappropriately decreased expression of the iron-regulatory hormone hepcidin. Hepcidin serves to decrease the export of iron from reticuloendothelial cells and absorptive enterocytes. Thus, HH patients demonstrate increased iron release from these cell types, elevated circulating iron, and iron deposition in vulnerable tissues. The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE.

REFERENCES

Robert E FlemingM.D. 

Department of Pediatrics, Saint Louis University School of Medicine

Cardinal Glennon Childrens Hospital, 1465 S. Grand Blvd.

St. Louis, MO 63104

eMail: flemingr@slu.edu