Hereditary Hemochromatosis: Pathogenesis, Diagnosi... [Gastroenterology. 2010] - PubMed result

Gastroenterology. 2010 Jun 10. [Epub ahead of print]

Hereditary Hemochromatosis: Pathogenesis, Diagnosis and Treatment.
Pietrangelo A.

Division of Medicine and Centre for Hemochromatosis, University Hospital of Modena, Modena, Vxia del Pozzo 71, 41100 Modena, Italy.

Abstract
In the late 1800s hemochromatosis was considered an odd autoptic finding. More than 1 century later, it was finally recognized as a hereditary, multi-organ disorder associated with a polymorphism that is common among Caucasians: a 845G-A change in HFE that results in C282Y in the gene product. Hemochromatosis is now a well-defined syndrome characterized by normal iron-driven erythropoiesis and the toxic accumulation of iron in parenchymal cells of liver, heart, and endocrine glands. It can be caused by mutations that affect any of the proteins that limit the entry of iron into the blood. In mice, deletion of the iron hormone hepcidin and any of 8 genes that regulate its biology, including Hfe, transferrin-receptor 2 ( Tfr2)and hemojuvelin(Hjv) (which all sense the accumulation of iron that hepcidin corrects) or ferroportin (Fpn) (the cellular iron-exporter down-regulated by hepcidin), causes iron overload but not organ disease. In humans, loss of TfR2, HJV, and hepcidin itself or FPN mutations result in full-blown hemochromatosis. Unlike these rare instances, in Caucasians, homozygotes for C282Y polymorphism in HFE are numerous, but they are only predisposed to hemochromatosis; complete organ disease develops in a minority, when these individuals abuse alcohol or from other unidentified modifying factors. HFE gene testing can be used to diagnose hemochromatosis, but analyses of liver histology and clinical features are still required to identify patients with rare, non-HFE forms of the disease. The role of hepcidin in the pathogenesis of hemochromatosis reveals its similarities to endocrine diseases such as diabetes and indicates new approaches to diagnosis and manage this common disorder in iron metabolism. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 20542038 [PubMed - as supplied by publisher]
Hereditary Hemochromatosis: Pathogenesis, Diagnosi... [Gastroenterology. 2010] - PubMed result