Hyperferritinemia and non-HFE hemochromatosis: differential diagnosis and workup

Hyperferritinemia is a common reason for referral to a hepatogastroenterologist. The most frequent causes are not associated with iron overload (e.g. inflammatory diseases, alcohol abuse, metabolic syndrome, etc.). However, hyperferritinemia can also be caused by a genetic variant in one of the iron regulatory genes, called hereditary hemochromatosis, often but not always associated with iron overload. A variation in the human Hemostatic Iron Regulator protein (HFE) gene is the most common genotype, but many other variants have been described. In this paper we discuss two cases of rare hyperferritinemia associated disorders, ferroportin disease and hyperferritinemia-cataract syndrome. We also propose an algorithm for evaluating hyperferritinemia, facilitating a correct diagnosis and preventing potentially unnecessary examinations and therapeutic actions.

Keywords: iron overload, ferroportin disease, hereditary hyperferritinemia-cataract syndrome.