Abstract

Background—The diagnosis of genetic haemochromatosis (GH) before iron overload has developed is difficult. However a convincing candidate gene for GH, HFE (previously HLA-H), has been described recently.

Aims—To determine the prevalence of the haemochromatosis associated HFE mutations C282Y and H63D in United Kingdom affected and control populations.

Methods—The prevalence of the HFE C282Y and H63D mutations was determined by polymerase chain reaction amplification and restriction enzyme digestion in a cohort of 115 well characterised patients with GH and 101 controls from the United Kingdom.

Results—One hundred and five of 115 (91%) patients with GH were homozygous for the C282Y mutation. Only one of 101 (1%) controls was homozygous for the C282Y mutation and this individual currently shows evidence of iron overload. Two of five patients who did not have either of the two described mutations of HFE had early onset iron overload (ages 16 and 24). One had a family history of cardiac failure and the second was subsequently hospitalised due to cardiac failure. These are the first phenotypic observations for patients without either C282Y or H63D mutation of HFE.

Conclusion—This simple genetic test promises to be a highly effective tool in the diagnosis of GH.