Diagnostic Evaluation of Hereditary Hemochromatosis (HFE and Non-HFE)

The management and understanding of hereditary hemochromatosis have evolved with recent advances in iron biology and the associated discovery of numerous genes involved in iron metabolism. HFE-related (type 1) hemochromatosis remains the most frequent form, characterized by C282Y mutation homozygosity. Rare forms of hereditary hemochromatosis include type 2 (A and B, juvenile hemochromatosis caused by HJV and HAMP mutation), type 3 (related to TFR2 mutation), and type 4 (A and B, ferroportin disease). The diagnostic evaluation relies on comprehension of the involved pathophysiologic defect, and careful characterization of the phenotype, which gives clues to guide appropriate genetic testing.