Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study

Background Although genotyping studies suggest that hereditary haemochromat osis is one of the most common genetic disorders in white people, it is sti ll thought of as an uncommon disease. Our aim was to test the hypothesis th at hereditary haemochromatosis is a disease often overlooked in patients wi th late-onset type 1 diabetes mellitus, a late manifestation of untreated i ron overload. Methods We did a retrospective study in which we genotyped for the C282Y an d H63D mutations in the haemochromatosis gene in 716 unselected Danish pati ents who developed type I diabetes mellitus after age 30 years and 9174 con trols from the general Danish population. We also screened for hereditary h aemochromatosis by assessment of transferrin saturation. Findings More patients with diabetes (n=9, relative frequency 1.26%, 95% CI 0.58-2.37) than controls (23, 0.25%, 0.16-0.38) were homozygous for C282Y (odds ratio 4.6, 2.0-10.1, p=0.0001). These patients had unrecognised signs of haemochromatosis. Transferrin saturation and ferritin concentrations ra nged from 57% to 102% and 17 mug/L to 8125 mug/L, respectively. Frequency o f compound heterozygosity (C282Y/H63D) did not differ between patients with diabetes (eight) and controls (131) (odds ratio 0.8, 95% CI 0.4-1.7). Posi tive and negative predictive values of transferrin saturation greater than 50%, in identification of C282Y homozygosity, were 0.26 and 1.00, respectiv ely. A saturation of less than 50% therefore excluded C282Y homozygosity, w hereas a saturation of more than 50% suggested C282Y homozygosity. Interpretation Measurement of transferrin saturation followed by genetic te sting could prevent liver and heart problems and improve life expectancy in patients with diabetes. Population screening before the onset of diabetes might improve the outlook of patients even further, but will be less cost e ffective.