Review article: the screening, diagnosis and optimal management of haemochromatosis

Abstract

Haemochromatosis was first recognized as a disease entity over a century ago and its hereditary nature recognized over 60 years ago. However it was only in late 1996 that the haemochromatosis gene was cloned and a single C282Y mutation confirmed as being the cause of all HLA-linked iron overload in Caucasian populations. Haemochromatosis is common, occurring in approximately 1 in 300 people in Caucasian populations, and untreated can cause serious morbidity and early death. However, the disease remains much underdiagnosed for reasons such as lack of awareness of the disease, the presence of normal liver function tests and the lack or non-specific nature of symptoms. A commercially available DNA-based test for the haemochromatosis gene is likely to be available in the near future but its place in the diagnosis and management of the disorder is not yet clear. Assessment of body iron stores by measurement of serum ferritin and transferrin saturation, hepatic iron stores and hepatic architecture by liver biopsy will remain important in the future. The haemochromatosis mutation itself has as yet no known influence on morbidity other than via iron loading and organ failure, in particular, hepatic cirrhosis. Thus, diagnosing patients before the development of hepatic cirrhosis is crucial because iron depletion by venesection treatment before the development of cirrhosis results in a normal life expectancy.