Objective: To identify the most appropriate testing strategy for genetic haemochromatosis in a liver clinic population by determining the ethnic distribution of the HFE mutations and the relationship between serum iron markers, hepatic siderosis and HFE genotype.
Design and setting: Observational study of 427 patients being investigated for abnormal liver function tests between 1997 and 2000 attending a liver clinic at a teaching district general hospital in south London, UK.
Methods: All patients were tested for H63D and C282Y gene mutations, and the ethnic origin was determined. Data were available for most patients for non-fasting serum iron, ferritin and transferrin saturation on presentation and fibrosis and siderosis scores from liver biopsy.
Results: The C282Y mutation was not detected in any patients of Asian or Afro-Caribbean origin but was found almost exclusively in northern Europeans, especially those classified as Celtic, one in seven of whom were heterozygous for this mutation. Three per cent of all the patients tested were C282Y homozygotes. The H63D mutation was distributed more widely. An elevated serum transferrin saturation was both a more sensitive and a more specific test for genetic haemochromatosis than either serum ferritin or iron. Significantly raised mean siderosis scores were found on liver biopsy in C282Y homozygote and C282Y/H63D compound heterozygote groups but not in wild-type, simple heterozygote, or H63D homozygote groups. Forty-five per cent of the C282Y homozygotes detected already had cirrhosis.
Conclusions: In a multiracial liver clinic population, previously undiagnosed C282Y homozygosity was found to be common (3% in our study) but restricted to those of northern European heritage, particularly those with Celtic ancestry. A serum transferrin saturation proved a better initial test to select patients for genotyping than serum iron or ferritin. Laboratory costs can be minimized with no loss of diagnostic sensitivity by selecting patients for genotyping based on northern European ethnic origin and raised serum transferrin saturation.