Background and objective: Iron overload is the result of many disorders and could lead to the development of organ damage and increased mortality. The recent description of new conditions associated with iron overload and the identification of the genetic defect of hereditary hemochromatosis prompted us to review this subject and to redefine the diagnostic criteria of iron overload disorders.
Evidence and information sources: The material examined in the present review includes articles published in the Journals covered by the Science Citation Index and Medline. The author has been working in the field of iron overload diseases for several years and has contributed ten of the papers cited in the references.
State of the art and perspectives: Iron overload can be classified on the basis of different criteria: route of access of iron within the organism, predominant tissue site of iron accumulation and cause of the overload. Excess iron can gain access by the enteral route, the parenteral route, and placental route during fetal life. The different distribution of iron within parenchymal or reticuloendothelial storage areas indicates different pathogenetic mechanisms of iron accumulation and has relevant implications in terms of organ damage and prognosis of the patients. Iron overload may be either primary, resulting from a deregulation of intestinal iron absorption as in hemochromatosis or secondary to other congenital or acquired conditions. Diagnosis of iron overload can be suspected on the basis of clinical data, high transferrin saturation and/or serum ferritin values. However, several hyperferritinemic conditions are not related to iron overload, but may imply severe disorders (inflammations, neoplasia) or a deregulation of ferritin synthesis (hereditary hyperferritinemia-cataract syndrome), and iron overload secondary to aceruloplasminemia, and the recently described dysmetabolic-associated liver iron overload syndrome, are characterized by low or normal transferrin saturation levels. Liver biopsy is still very useful in the diagnostic approach to iron overload disorders, by defining the amount and the distribution of iron within the liver. The analysis of HFE gene mutations (C282Y and H63D) is a simple and strong tool in the diagnostic work out of iron overload conditions.