Inherited HFE-unrelated hemochromatosis in Italian families

Hemochromatosis (HH) is usually caused by the homozygous state for C282Y mu tation in the HFE gene. A minority of iron loaded patients have no mutation s in this gene. An infrequent subset shows an early-onset aggressive disord er, denoted juvenile hemochromatosis (JH), which has no linkage to 6p. In t his report we describe six patients from three unrelated Italian families, four men and two women, aged 21 to 44 with the typical hemochromatosis phen otype, who are homozygous for the wild type allele at the HFE gene. In two families the disorder is unlinked to 6p; in one family some features of the juvenile form are seen, but linkage to 6p is not excluded. Our results poi nt to genetic forms of hemochromatosis not associated with HFE and raise th e problem of whether non-HFE hemochromatosis in Italy is related to the "ju venile" form. They also emphasize the importance of phenotypic as well as g enetic diagnosis of HH.