Hereditary Haemochromatosis: Recent Advances in Biology and Management

Abstract

Hereditary haemochromatosis (HH) is an autosomal recessive disorder leading to excessive absorption of dietary iron. The gene affected in the common variety has recently been identified near the HLA-A locus on chromosome 6 and designated HFE. The HFE mutation, C282Y, responsible for most cases of HH is found in as many as 8–18% of people of European descent; 6–32 per 1000 are therefore homozygous, but only a variable proportion accumulate enough iron to develop organ damage with the associated clinical manifestations. Clinical expression depends on the amount of absorbable iron in the diet, the amount of iron being lost (greater in women through menstruation and pregnancies) and the severity of the genetic defect. The excess iron can be removed by serial phlebotomies. In symptomatic individuals this reverses some of the manifestations and prolongs survival significantly; if treatment is instituted before symptoms appear all manifestations are prevented. The objective must therefore be to identify and treat affected individuals in the presymptomatic stage. In this context, the role of population screening is currently being debated.

Keywords:

• Hereditary haemochromatosis
• biology
• diagnosis
• management