Genetic Hemochromatosis, a Celtic Disease: Is It Now Time for Population Screening?

Abstract

In populations of northern European ancestry, hereditary hemochromatosis (HH) is tightly linked to mutations within the hemochromatosis gene (HFE gene). Over 93% of Irish HH patients are homozygous for the HFE gene C282Y mutation, providing a reliable diagnostic marker of the disease in this population. However, the prevalence of the C282Y mutation and that of the second HFE gene mutation, H63D, have yet to be determined within the Irish population. 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 randomly selected newborn screening cards and analyzed for the C282Y and H63D mutations within the HFE gene. Complete results were obtained from 800 cards. Mutations were identified in 364 (46%) neonates. Eight (1%) neonates were 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 mutations, i.e., compound heterozygous. Allele frequencies for C282Y and H63D were 11% and 15%, respectively. The high C282Y allele frequency in the Irish population together with its close linkage to HH indicate that C282Y genotyping is the preferred screening strategy for this disease in Ireland.

Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation

“…13,38,[62][63][64][65][66][67] Six studies were prospective cohort studies, 38,62,63,[65][66][67] with two including a control group. 38,62 The other two studies were a retrospective cohort study 13 and a cross-sectional case-control study.…”

“…38,62 The other two studies were a retrospective cohort study 13 and a cross-sectional case-control study. 64 The participants in the studies varied depending upon the rationale for the study, including people diagnosed with haemochromatosis, 13,38,62 people attending a blood donation service, 65,67 those on registers of newborn children 63 or heart attack sufferers, 64 and those attending for routine blood screening. 66 Control groups included healthy blood donors, 38 people registered with general practitioners 64 and people on bone marrow registers.…”

“…Prevalence data for the general population originated from several cohorts including healthy blood donors, 38,65,67 a register of newborn children, 63 general practitioner populations, 64 people on bone marrow registers 62 and people providing blood specimens for routine screening. 66 Inevitably the variations in these groups may have some effect on the prevalence rates reported.…”

Genetic polymorphisms and the progression of liver fibrosis: A critical appraisal

“…It is approximately 10% in subjects of Celtic descent, whereas the prevalence is much lower in subjects from southern Europe. 105,106 Patients heterozygous for C282Y mutation show normal or only slightly elevated hepatic iron content and do not spontaneously develop liver injury. 107 However, these patients could theoretically be more susceptible to the development of liver disease when exposed to agents such as hepatitis viruses.…”

Health-related quality of life in a racially diverse population screened for hemochromatosis: results from the Hemochromatosis and Iron Overload Screening (HEIRS) study

“…2 Although populationbased HFE screening may be a justifiable way to identify individuals at risk, it is important to evaluate screening risks and benefits, including the impact of an HFE screening program on psychosocial status or quality of life. 3,4 Previous studies examining acceptability of genetic testing for hemochromatosis note HFE genotyping is acceptable to many 5 or even most 6 individuals offered testing, and studies have not shown deleterious psychosocial outcomes. [7][8][9] This has led to a preliminary conclusion that population-based screening should not be discouraged on the basis of potential adverse psychosocial effects.…”