DISTRIBUTION OF TRANSFERRIN SATURATION IN AN AUSTRALIAN POPULATION - RELEVANCE TO THE EARLY DIAGNOSIS OF HEMOCHROMATOSIS

Background & Aims: An elevated transferrin saturation is the earliest phenotypic abnormality in hereditary hemochromatosis. Determination of transferrin saturation remains the most useful noninvasive screening test for affected individuals, but there is debate as to the appropria te screening level. The aims of this study were to estimate the mean t ransferrin saturation in hemochromatosis heterozygotes and normal indi viduals and to evaluate potential transferrin saturation screening lev els. Methods: Statistical mixture modeling was applied to data from a survey of asymptomatic Australians to estimate the mean transferrin sa turation in hemochromatosis heterozygotes and normal individuals. To e valuate potential transferrin saturation screening levels, modeling re sults were compared with data from identified hemochromatosis heterozy gotes and homozygotes. Results: After removal of hemochromatosis homoz ygotes, two populations of transferrin saturation were identified in a symptomatic Australians (P < 0.01). In men, 88.2% of the truncated sam ple had a lower mean transferrin saturation of 24.1%, whereas 11.8% ha d an increased mean transferrin saturation of 37.3%. Similar results w ere found in women, A transferrin saturation threshold of 45% identifi ed 98% of homozygotes without misidentifying any normal individuals. C onclusions: The results confirm that hemochromatosis heterozygotes for m a distinct transferrin saturation subpopulation and support the use of transferrin saturation as an inexpensive screening test for hemochr omatosis. In practice, a fasting transferrin saturation of greater tha n or equal to 45% identifies virtually all affected homozygous subject s without necessitating further investigation of unaffected normal ind ividuals.