A new form of hereditary iron overload unlinked to known hereditary haemochromatosis genes

Hereditary iron overload conditions are normally caused by mutations in the HFE gene or other genes involved in the regulation of iron homeostasis. We describe a family with an iron overload condition with apparent autosomal dominant inheritance and phenotypic similarities to the classical form of ferroportin disease. The condition is characterised by elevated serum ferritin levels with normal or mildly elevated transferrin saturation and prominent iron deposition in both Kupffer cells and hepatocytes. Serum hepcidin levels were elevated in affected members of the pedigree and correlated with serum ferritin concentration. No pathogenic variants were identified in HFE or SLC40A1, the gene encoding ferroportin. Whole genome linkage analysis showed maximal linkage of the iron overload phenotype to regions on chromosomes 1, 3, 12, 18 and 19, indicating that affected members of this family do not have a variant form of ferroportin disease and are likely to have a new form of hereditary iron overload due to defects in another gene.