C282Y and H63D mutations of the haemochromatosis gene in patients with iron overload

Objective: to determine the relevance of C282Y and H63D mutations of HEF ge ne in patients with iron overload. Patients and methods: patients with iron overload referred to our Liver Uni t were included in the study. The association of mutations to different dia gnosis and their impact on the severity of the hepatopathy were explored. S ensitivity, specificity and positive and negative predictive values of muta tions for the diagnosis of haemochromatosis were determined. Results: the study included 78 patients with iron overload. The control gro up included 21 patients of similar age and sex ratio without iron overload nor hepatopathy. Twenty three patients had haemochromatosis, 22 alcoholic l iver disease and 33 other diseases unrelated to iron metabolism. Seventy th ree per cent of patients with haemochromatosis were homozygous for the C282 Y mutation. All the C282Y homozygous subjects had also haemochromatosis. Fi fty three per cent of patients with alcoholic hepatopathy had some kind of mutation. This has been also observed in 70% of patients with iron-unrelate d diseases. Such percentage was significantly greater than in the control g roup (24% with H63D mutation). C282Y homozygosity in patients with iron ove rload had a sensitivity of 73.9%, a specificity of 100%, a positive predict ive value of 100% and a negative predictive value of 89.6%. Conclusions: in our population, as in all the Western countries, haemochrom atosis is mainly associated to homozygous C282Y mutation. The high frequenc y of mutations in patients with iron overload and without haemochromatosis suggests the involvement of such mutations in iron overload.