CLASSIFICATION AND DIAGNOSIS OF IRON OVERLOAD

Background and Objective. Iron overload is the result of many disorder s and could lead to the development of organ damage and increased mort ality. The recent description of new conditions associated with iron o verload and the identification of the genetic defect of hereditary hem ochromatosis prompted us to review this subject and to redefine the di agnostic criteria of iron overload disorders. Evidence and information sources. The material examined in the present review includes article s published in the journals covered by the Science Citation index(R) a nd Medline(R). The author has been working in the field of iron overlo ad diseases for several years and has contributed ten of the papers ci ted in the references. State of the art and Perpectives. Iron overload can be classified on-the basis of different criteria: route of access of iron within the organism, predominant tissue site of iron accumula tion and cause of the overload. Excess iron can gain access by the ent eral route, the parenteral route, and placental route during fetal lif e. The different distribution of iran within parenchymal or reticuloen dothelial storage areas indicates different pathogenetic mechanisms of iron accumulation and has relevant implications in terms of organ dam age and prognosis of the patients. Iron overload may be either primary , resulting from a deregulation of intestinal iron absorption as in he mochromatosis 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. Howeve r, several hyperferritinemic conditions are not related to iron overlo ad, but may imply severe disorders (inflammations, neoplasia) or a der egulation of ferritin synthesis (hereditary hyperferritinemia-cataract syndrome), and iron overload secondary to aceruloplasminemia, and the recently described dysmetabolic-associated liver iron overload syndro me, are characterized by low or normal transferrin saturation levels. Liver biopsy is still very useful in the diagnostic approach to iron o verload 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 overlo ad conditions. (C)1998, Ferrata Storti Foundation.