ABSTRACT
Since the discovery of the HFE gene of hereditary haemochromatosis in 1996 several new genetic defects have been identified, enabling explanation of the cause and variety of this disease. To date, at least 5 major types of hereditary haemochromatosis have been recognised. All these genes encode for proteins that are involved in metabolic pathways relevant to hepcidin synthesis in the liver. Hepcidin is a small protein that regulates the activity of the iron exporting protein ferroportin in the basolateral membrane of duodenal cells and the cell membrane of macrophages and thereby controls serum iron concentration. Plasma hepcidin concentration is elevated in body iron excess and by inflammatory stimuli, and is lowered in erythroid iron demand, hypoxia and most types of hereditary haemochromatosis. It is the clinician's task to diagnose hereditary haemochromatosis before irreversible tissue damage arises and at the same time to differentiate between ongoing iron accumulation and increasingly prevalent disorders with elevated serum ferritin such as the metabolic syndrome.
