The clinical manifestations of chronic iron overload

Primary or genetic haemochromatosis is an inherited disease characterized by an inappropriate degree of iron absorption with accumulation of excessive amounts of tissue iron. Parenchymal iron accumulation results in the typical clinical features of the disease including hepatic cirrhosis, diabetes, testicular atrophy and skin pigmentation. The disease is inherited in an autosomal recessive manner. The gene for the disease has not been identified but is tightly linked to the A locus of the histocompatibility complex on chromosome 6. The approximate homozygote frequency in Caucasians is 0.3% with an equal sex ratio. Excessive body iron stores have been described in a number of other conditions, particularly alcoholic liver disease. There is increasing evidence that many of these individuals are in fact also suffering from genetic haemochromatosis. Diagnostic tests including serum iron, transferrin saturation, serum ferritin and liver iron concentration make it possible to detect sufferers of the disease. Screening relatives of affected individuals with these tests allows a diagnosis to be made before permanent tissue damage has occurred. Removal of excess iron stores by repeated phlebotomy is the primary treatment. If iron is removed before significant tissue damage has occurred, the complications and natural course of the disease will be prevented provided reaccumulation of iron does not occur. Excessive iron accumulation with resultant organ damage also occurs in anaemias associated with ineffective erythropoiesis and after excessive parenteral iron administration or repeated blood transfusions. Similar clinical features may be seen. Chelation therapy is the mainstay of treatment in these cases where long-term venesection is not possible.