In populations of northern European ancestry, hereditary hemochromatosis (H
H) is tightly linked to mutations within the hemochromatosis gene (HFE gene
). Over 93% of Irish HH patients are homozygous for the HFE gene C282Y muta
tion, providing a reliable diagnostic marker of the disease in this populat
ion. However, the prevalence of the C282Y mutation and that of the second H
FE gene mutation, H63D, have yet to be determined within the Irish populati
on. The objective of this study was to identify the true prevalence of the
genetic form of HH in the Irish population. DNA was extracted from 1002 ran
domly selected newborn screening cards and analyzed for the C282Y and H63D
mutations within the HFE gene. Complete results were obtained from 800 card
s. Mutations were identified in 364 (46%) neonates. Eight (1%) neonates wer
e homozygous for C282Y and 8 (1%) were homozygous for H63D. One hundred and
fifty-five (19%) neonates were C282Y heterozygous and 226 (28%) were H63D
heterozygous. Of these, 33 (4%) carried one copy of both C282Y and H63D mut
ations, i.e., compound heterozygous. Allele frequencies for C282Y and H63D
were 11% and 15%, respectively. The high C282Y allele frequency in the Iris
h population together with its close linkage to HH indicate that C282Y geno
typing is the preferred screening strategy for this disease in Ireland.