H63D homozygosity: the clinical and biochemical burben in patients with haemachromatosis

Background: Hereditary Haemochromatosis is an inherited disorder associated with increased iron absorption. C282Y homozygosity has been found in 93% of Irish haemachromatosis patients. The clinical significance of H63D is less clear.

Aims: To study the biochemical and clinical burden associated with H63D mutation in patients attending a single centre.

Methods: Medical notes were reviewed for standard demographic details, biochemical data and histology where available.

Results: There were 210 Haemochromatosis patients and 36 (17%) were homozygous for H63D (Male; n=30; mean age 52 yr: Female; n=6; mean age 49 yr). Serum ferritin levels were higher than normal in 24 (66%) patients [range332–3000; mean 734; normal range 20–300]. Transferrin saturation was increased in 26 (70%) patients [range 45%-75%; mean 46%]. High glucose and HBA1C levels were seen in 16 (44%) patients. Abnormalities in liver blood profile were noted in 23 (64%) patients. Liver biopsy was performed in 11 patients, six (54%) had evidence of siderosis (grade 2 to 4). None had cirrhosis.

Conclusions: H63D homozygosity is associated with a high rate of clinically significant disease (High Iron indices 66–70%, Liver dysfunction 64%, Diabetes 44%). H63D homozygotes have increased risk of diabetes. The relationship between the gene, insulin resistance and diabetes warrants further study