Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.

Background/aims: In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH.

Methods: Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS).

Results: The best predictive multivariable model forecasted 45% of variation of the serum ferritin levels. In this model severity of iron overload in the proband significantly predicted serum ferritin levels in FDFM. Other significant determinants in this model consisted of C282Y homozygosity, compound heterozygosity, age at testing for serum ferritin and supplemental iron intake, whereas a low body mass index showed a protective effect.

Conclusions: This study provides a model to assess the risk of development of iron overload for relatives of probands with HH. These results might be instrumental in the development of an optimal strategy for future family screening programs.