BACKGROUND: Hereditary haemochromatosis (HH) is one of the commonest genetic disorders in European populations. Transferrin saturation (TFS) measurement has been advocated as a phenotypic screening test to improve detection. We undertook a prospective study to examine the value of routine TFS measurement in detecting new cases of HH in unselected liver clinic attenders. METHODS: Non-fasting TFS was measured in new patients. HH mutations were determined in those with elevated TFS (>45%) and all who underwent liver biopsy. Liver biopsy was performed in 349 patients, including all found to be C282Y homozygotes or compound heterozygotes. RESULTS: Of 667 new patients attending over 5 years, 156 had TFS >45% and 18 had significant mutations (12 C282Y homozygotes and six compound heterozygotes). Eleven of the 12 C282Y homozygotes identified had an elevated TFS and 10 had significant hepatic siderosis. Only two of the six compound heterozygotes had an elevated TFS and hepatic siderosis. CONCLUSIONS: The prevalence of new HH cases in patients of European origin attending a liver clinic, detected by phenotypic screening over a 5-year period, was 2.8%. All were identified by a TFS cut off >45%, but TFS >60% provided the best combination of sensitivity and specificity for detecting C282Y homozygosity.
BACKGROUND:Hereditary haemochromatosis (HH) is one of the commonest genetic disorders in European populations. Transferrin saturation (TFS) measurement has been advocated as a phenotypic screening test to improve detection. We undertook a prospective study to examine the value of routine TFS measurement in detecting new cases of HH in unselected liver clinic attenders. METHODS: Non-fasting TFS was measured in new patients. HH mutations were determined in those with elevated TFS (>45%) and all who underwent liver biopsy. Liver biopsy was performed in 349 patients, including all found to be C282Y homozygotes or compound heterozygotes. RESULTS: Of 667 new patients attending over 5 years, 156 had TFS >45% and 18 had significant mutations (12 C282Y homozygotes and six compound heterozygotes). Eleven of the 12 C282Y homozygotes identified had an elevated TFS and 10 had significant hepatic siderosis. Only two of the six compound heterozygotes had an elevated TFS and hepatic siderosis. CONCLUSIONS: The prevalence of new HH cases in patients of European origin attending a liver clinic, detected by phenotypic screening over a 5-year period, was 2.8%. All were identified by a TFS cut off >45%, but TFS >60% provided the best combination of sensitivity and specificity for detecting C282Y homozygosity.