Iron Overload Introduction
Iron overload is a serious, potentially fatal condition characterized by the deposition of iron within the body (hemosiderosis). In severe iron overload, deposition in the heart, liver, and endocrine system leads to functional impairment of these organs, and reduced life expectancy.
Under normal conditions, transferrin binds iron tightly and protects tissues from its damaging effects, but the total iron-binding capacity of transferrin is limited. Under conditions of iron overload, transferrin becomes saturated and iron released from cells (macrophages, enterocytes) will bind to other proteins or low molecular weight organic molecules to form non-transferrin-bound iron.
Hepatic iron correlates with survival
Adapted with permission [1]
Iron overload is a potentially deadly condition. A study of patients with thalassemia major demonstrated an inverse correlation between liver iron concentration and survival. High liver iron levels (iii) were associated with a significantly greater mortality rate than low (i) or moderate (ii) iron levels. High iron was defined as >15 mg Fe/g of liver dry weight (dw); moderate 7-15 mg Fe/g dw; and low <7 mg Fe/g dw.
Since the human body possesses no mechanism for active iron excretion, iron overload is an inevitable consequence of iron loading. Iron overload can be classified as primary (genetic), if caused by a deficiency in the regulation of iron balance (eg hereditary hemochromatosis), or secondary (acquired) if caused by another disorder or as a result of its treatment (eg excessive absorption of dietary iron or blood transfusions).
Hereditary hemochromatosis is the most frequently inherited human disease [2] and is the most common genetic disease in individuals of Northern European origin, with a prevalence of three per 1000 Caucasians [3]. Transfusional iron overload is an inevitable outcome in patients who receive repeated blood transfusions, unless iron levels are controlled. Other disorders, where excess iron can play a role, include alcoholic liver disease [4] and chronic hepatitis C infection [5].
Fortunately, there are effective treatments for iron overload. For patients with hereditary hemochromatosis, phlebotomy currently provides an effective means of reducing heme-bound iron. For patients with iron overload due to transfusions, as well as those with acute iron poisoning and iron-related heart disease, iron chelation therapy is an effective way to remove the excess iron with a subsequent significant improvement in life expectancy.
  References
(1) Telfer PT, Prestcott E, Holden S, et al. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol. 2000;110(4):971-7.
(2) Sheth S, Brittenham GM. Genetic disorders affecting proteins of iron metabolism: clinical implications. Annu Rev Med. 2000;51:443-64.
(3) Douabin V, Moirand R, Jouanolle A, et al. Polymorphisms in the HFE gene. Hum Hered. 1999;49(1):21-6.
(4) Pietrangelo A. Iron-induced oxidant stress in alcoholic liver fibrogenesis. Alcohol. 2003;30(2):121-9.
(5) Farinati F, Cardin R, De Maria N, et al. Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol. 1995;22(4):449-56.
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