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Hemochromatosis type 4 is an atypical hemochromatosis characterized by dominant inheritance, increased serum ferritin, normal transferrin saturation, and prevalent iron deposition in the reticuloendothelial (RE) cells rather than in hepatocytes. Heterozygous missense mutations of the iron export

Objectives: To test the feasibility of adopting and evaluating a systematic case-finding approach to the early diagnosis of hereditary haemochromatosis (HHC) in primary care, and to estimate the prevalence of presenting conditions for which HHC testing could be offered. Methods: Systematic identification of, and genotyping for, C282Y and H63D mutations in patients presenting in primary care with possible symptoms of HHC during a 4-week period to 1 of 14 doctors in Oxfordshire. Results: From a total of 4,022 consultations, 169 (4.2%; 95% CI: 3.6–4.8) adult patients had possible symptoms of HHC. Of these, 88 (2.2%; 95% CI: 1.7–2.6) were aged 25–70 and were offered genotyping for HHC, of whom 60 agreed to be tested. There were no C282Y homozygotes (0%; 95% CI: 0–6.0), no C282Y/H63D compound heterozygotes (0%; 95% CI: 0–6.0), 2 H63D homozygotes with normal iron indices (3.3%%; 95% CI: 0.4–11.5) and 3 C282Y heterozygotes (5.0%; 95% CI: 1.0–13.9). Conclusions: This study raises doubts about a case-finding approach to early diagnosis of HHC in primary care. The non-specific nature and high prevalence of possible symptoms of HHC in primary care mean that many patients would require testing to identify a single case. Whether this offers a more cost-effective alternative to population screening requires further study.

Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by mutations in the HFE gene that mainly affects populations of European descent. Recently a novel mutation (IVS5+1 G→A) has been described in a Vietnamese patient with HH that was not detected in a European control population. We have developed a novel method to screen for this mutation based on restriction enzyme digestion of a PCR product using a modified forward primer. We have screened 314 Vietnamese people from several ethnic groups and 154 people from Thailand for this mutation and have detected two heterozygotes in the Vietnamese subjects (allele frequency 0.003). Analysis of these heterozygotes indicates that the mutation is on the same haplotype as that found in the original proband. Screening for the widely distributed HFE mutation, H63D, gave an allele frequency of 0.049 in the Vietnamese subjects and 0.032 in the subjects from Thailand. This is the first report of H63D allele frequencies in these populations. We suggest that the presence of the IVS5+1 G→A and H63D mutations should be considered when investigating iron overload in Vietnamese patients and those of mixed origin as co-inheritance of both mutations is likely to be a risk factor for iron overload.