Most hereditary hemochromatosis (HH) patients are homozygous for the C282Y 
mutation of the HFE gene. Nevertheless, penetrance of the disease is very 
variable. In some patients, penetrance can be mediated by concomitant mutations 
in other iron master genes. We evaluated the clinical impact of hepcidin (HAMP) 
and hemojuvelin mutations in a cohort of 100 Spanish patients homozygous for the 
C282Y mutation of the HFE gene. HAMP and hemojuvelin mutations were evaluated in 
all patients by bidirectional direct cycle sequencing. Phenotype-genotype 
interactions were evaluated. A heterozygous mutation of the HAMP gene (G71D) was 
found in only one out of 100 cases. Following, we performed a study of several 
members of that family, and we observed several members had a digenic 
inheritance of the C282Y mutation of the HFE gene and the G71D mutation of the 
HAMP gene. This mutation in the HAMP gene did not modify the phenotype of the 
individuals who were homozygous for the C282Y mutation. One other patient 
presented a new polymorphism in the hemojuvelin gene, without consequences in 
iron load or clinical course of the disease. In conclusion, HAMP and hemojuvelin 
mutations are rare among Spanish HH patients, and their impact in this 
population is not significant.