Importance of establishing appropriate local reference values for the screening of hemochromatosis: a study of three different control populations and 136 hemochromatosis family members. Hemochromatosis Clinical and Research Group.

Hemochromatosis is a human leukocyte antigen-linked (HLA-linked), potentially lethal disorder of iron metabolism with a high prevalence in white populations albeit an autosomal recessive mode of transmission. The diagnosis and treatment at early stages of the disease are critical to the prevention of the morbidity and mortality caused by the iron overload. After the identification of the first cases of hemochromatosis in Portugal, a screening program was started with a systematic search for the disease among family members of the patients, as well as in subjects from the normal population. In this study we analyze the results obtained with a total of 136 family members from 15 different families and 353 control subjects from three different villages, two in the north and one in the south of Portugal. We establish reference values for the biochemical tests used in the screening for iron overload and analyze the factors that affect those results. Besides sex-related differences, factors that were found to influence biochemical parameters most significantly included age and levels of daily alcohol intake. In addition, differences in iron status were identified between the populations from the regions in the north and the south of the country. We estimate, by HLA typing and family studies, a gene frequency for hemochromatosis of 0.14 that corresponds to a frequency of homozygotes and heterozygotes of 0.019 and 0.24, respectively.