3 years ago

The ferroportin disease: pathogenesis, diagnosis and treatment.

Antonello Pietrangelo
The Ferroportin Disease is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of commonest cause of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In the ferroportin disease, loss-of-function mutations of FPN1 limit but do not impair iron-export in enterocytes, but severely affects iron-transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum transferrin (i.e. inappropriately low transferrin saturation and tendency to anemia at menarche or after intense bloodletting. The hallmark of the ferroportin disease is marked iron accumulation in hepatic Kupffer cells. Numerous FD-associated mutations have been reported worldwide, with a few occurring in different populations and more commonly reported (e.g. Val192del, A77D and G80S). FPN1 polymorphisms also represent the gene variants most commonly responsible for hyperferritinemia in Africans. Differential diagnosis includes mainly hereditary hemochromatosis, the syndrome commonly due to either HFE or TfR2, HJV, HAMP and, in rare instances, FPN1 itself. Here, differently from the ferroportin disease, hyperferritinemia associates with high transferrin saturation, iron-spared macrophages and progressive parenchymal cell iron load. Abdominal MRI, the key non-invasive diagnostic tool for the diagnosis of ferroportin disease, shows the characteristic iron loading "SSL triad" (spleen, spine and liver). Non-aggressive phlebotomy regimen is recommended with careful monitoring of transferrin saturation and hemoglobin due to the risk of anemia. Family screening is mandatory since siblings and offspring have 50% chance of carrying the pathogenic mutation.

Publisher URL: http://doi.org/10.3324/haematol.2017.170720

DOI: 10.3324/haematol.2017.170720

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