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.