Edwards C Q, Griffen L M, Goldgar D, Drummond C, Skolnick M H, Kushner J P
Department of Internal Medicine, University of Utah College of Medicine, Salt Lake City 84132.
N Engl J Med. 1988 May 26;318(21):1355-62. doi: 10.1056/NEJM198805263182103.
There is evidence that iron loading and organ damage can be prevented in patients with hemochromatosis if prophylactic phlebotomy is employed early in the disease--findings emphasizing the importance of early detection before clinical signs occur. This study was designed to determine the efficacy of transferrin saturation as a screening tool for hemochromatosis and to assess the frequency of homozygosity for the HLA-linked hemochromatosis gene in a healthy population. We screened 11,065 presumably healthy blood donors (5840 men and 5225 women). Donors with transferrin saturations of 62 percent or more after an overnight fast were considered potential homozygotes and were asked to undergo liver biopsy and pedigree analysis. The frequency of values for transferrin saturation of 62 or higher in men was 0.008 and in women 0.003. Thirty-eight persons with values higher than 62 were studied in detail; 35 underwent liver biopsy. Liver iron stores ranged from normal to markedly increased. Twelve siblings with an identical HLA match to a proband underwent liver biopsy, and 11 had increased liver iron stores. According to likelihood analysis of the pedigrees, 26 of the 38 probands were homozygotes, and 12 were heterozygotes. The estimated frequency of homozygosity was based on the data in men, because the threshold value of 62 for the transferrin saturation identified only half as many female homozygotes as expected. The frequency of homozygosity was 0.0045, corresponding to a gene frequency of 0.067. The value of population screening is demonstrated in these studies by the detection of homozygotes before clinical manifestations of hemochromatosis occur.
有证据表明，如果在血色素沉着症患者疾病早期采用预防性放血疗法，铁负荷和器官损害是可以预防的——这一发现强调了在临床症状出现之前早期检测的重要性。本研究旨在确定转铁蛋白饱和度作为血色素沉着症筛查工具的有效性，并评估健康人群中与HLA相关的血色素沉着症基因纯合子的频率。我们对11,065名推测健康的献血者（5840名男性和5225名女性）进行了筛查。空腹过夜后转铁蛋白饱和度达到或超过62%的献血者被视为潜在纯合子，并被要求进行肝活检和系谱分析。男性中转铁蛋白饱和度达到或高于62的频率为0.008，女性为0.003。对38名转铁蛋白饱和度高于62的人进行了详细研究；35人接受了肝活检。肝脏铁储存量从正常到明显增加不等。12名与先证者HLA匹配相同的兄弟姐妹接受了肝活检，其中11人肝脏铁储存量增加。根据系谱的似然性分析，38名先证者中有26名是纯合子，12名是杂合子。纯合子频率的估计基于男性数据，因为转铁蛋白饱和度62的阈值识别出的女性纯合子数量仅为预期的一半。纯合子频率为0.0045，对应基因频率为0.067。这些研究通过在血色素沉着症临床表现出现之前检测到纯合子，证明了人群筛查的价值。
