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Editorial
. 2011 Apr;96(4):485-8.
doi: 10.3324/haematol.2011.042036.

Novel observations in hereditary hemochromatosis: potential implications for clinical strategies

Dorine W Swinkels, Robert E Fleming
Editorial

Novel observations in hereditary hemochromatosis: potential implications for clinical strategies

Dorine W Swinkels et al. Haematologica. 2011 Apr.
No abstract available

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Figures

Figure 1.
Figure 1.
Putative iron regulatory pathways of hepatocyte hepcidin synthesis. This proposed model depicts two iron signals to hepcidin, one mediated by intracellular iron stores (Fe) and the other by ferri-transferrin (Tf-Fe2). Hepatocellular iron stores increase the expression of bone morphogenetic protein 6 (BMP6), which serves as an autocrine factor by interacting with surface BMP receptors. Hemojuvelin (HJV) is a BMP co-receptor which augments BMP binding. The consequent activation of intra-cellular SMAD proteins transduces a signal to increase hepcidin transcription. Under low iron conditions matriptase-2 (scissors) cleaves HJV from the cell surface, weakening the BMP6 signal. Extracellular Tf-Fe2 mediates a second iron signal. In this schema Tf-Fe2 displaces HFE from TfR1. HFE is then freed to interact with transferrin receptor 2 (TfR2). The HFE-TfR2 complex activates hepcidin transcription via MAPK and/or BMP/SMAD signaling. These pathways have recently been reviewed.
Figure 2.
Figure 2.
Proposed diagnostic and therapeutic algorithm for patients with suspected hemochromatosis. Orange boxes indicate the parts of the guideline for which the novel observations of the two publications in this issue might provide opportunities for improvement. * in case of heterozygosity for the C282Y mutations start searching for rare mutations in HFE in the other allele. Serum hepcidin/ferritin ratio may contribute to prioritization of order of gene investigations. If mutations are present the work-up is similar to that for HFE hemochromatosis with respect to phlebotomy, screening relatives, and periodic screening of the liver in the case of liver cirrhosis. ^ Low ferritin targets may lead to excessive iron absorption. Measurement of hepcidin could have a role in monitoring phlebotomy and to assess the ferritin target and frequency of phlebotomy. Figure adapted from van Bokhoven et al.
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