Association Between Mutations in the HFE Gene for Hereditary Haemochromatosis with Iron Stores on Initial Presentation, and Subsequent Venesection Requirements

Background: Hereditary Haemochromatosis is an autosomal recessive disorder characterised by increased iron stores and increased deposition of iron in organs such as the liver. It has been shown that patients with Haemochromatosis have mutations in the HFE gene. The most frequently identified mutations are the C282Y and H63D substitution mutations, which are associated with increased iron absorption from the gastrointestinal tract. The standard treatment for this condition is the removal of blood by venesection/phlebotomy. We speculated that different mutation profiles are associated with different degrees of iron overload, and subsequently varying requirements for venesection.

Aims: (1) To examine the association between different mutation profiles and iron stores in Hereditary Hemochromatosis on initial presentation, and (2) To evaluate the association between different mutation profiles and initial venesection requirements to achieve an internationally accepted treatment goal (Ferritin of ≤50ng/mL).

Methods: The patients evaluated attended the Haemochromatosis Clinic at a University College Hospital, Galway. Data was collected from a database and a retrospective chart review. All patients had initial assessment and subsequent treatment according to standard management protocol. This included measurement of iron stores, gene mutation studies, liver biopsy if indicated, and a standardised venesection programme.

Results: To date 134 patients have been included in the study, of which 94 (70.1%) are men and 40 (29.9%) are female. The average age on presentation was 48 years, with a range from 14 to 86 years. Iron stores (ferritin levels and transferrin saturation) were significantly higher in C282Y homozygotes on presentation when compared to other groups (C282Y/H63D compound heterozygotes and H63D homozygotes) (p<0.05). The mean number of units removed per patient on initial presentation to achieve a ferritin of <50ng/mL was 18.48 in C282Y homozygotes, and 7.95 in other groups (p<0.001). Conclusion: When compared with other patient groups, patients who are homozygous for the C282Y mutation have significantly higher iron stores on presentation, and subsequently require more phlebotomy/venesection to achieve treatment goals.