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.

Review article: iron disturbances in chronic liver diseases other than haemochromatosis – pathogenic, prognostic, and therapeutic implications

“…Phlebotomy has been the standard method of treating iron overload in patients with hereditary haemochromatosis, and oral iron chelation therapy has been a substitute for phlebotomy in individuals intolerant of the procedure . Iron removal by phlebotomy has decreased the surrogate markers of oxidative stress (modified serum proteins) and reduced the serum level of the pro‐fibrotic cytokine, transforming growth factor‐beta 1 (TGF‐β1) .…”

Extended haplotype analysis in the HLA complex reveals an increased frequency of the HFE-C282Y mutation in individuals with multiple sclerosis

“…The HH phenotype is characterised by the progressive accumulation of iron in tissues because of hyper-absorption and can result in damage to vital organs (liver, heart and pancreas) and death if untreated (George and Powell 1997). The first genetic association for HH and MS was with HLA-A*3 (Jersild et al 1972;Simon et al 1976).…”

A simple, highly sensitive and improved method for the measurement of bleomycin-detectable iron: the ‘catalytic iron index’ and its value in the assessment of iron status in haemochromatosis

“…There are clinicians who advocate that the aim of venesection should be to maintain low serum ferritin levels (less than 50-100 ng\ml) [30]. Elevated CII values were often observed in plasma taken from haemochromatosis patients, and indeed were found to show correlations with serum iron and transferrin saturation values, but only when these values were above the normal, physiological range.…”