Bulaj Z J, Ajioka R S, Phillips J D, LaSalle B A, Jorde L B, Griffen L M, Edwards C Q, Kushner J P
Department of Medicine, University of Utah School of Medicine, Salt Lake City, USA.
N Engl J Med. 2000 Nov 23;343(21):1529-35. doi: 10.1056/NEJM200011233432104.
Hemochromatosis occurs in approximately 5 white people per 1000 and is usually due to homozygosity for mutations in the HLA-linked HFE gene. Although screening has been proposed, the proportion of homozygotes with conditions related to hemochromatosis is uncertain.
We studied the prevalence of disease-related conditions among relatives of probands with hemochromatosis. We identified probands who presented to a clinic with signs or symptoms of hemochromatosis or who had elevated transferrin-saturation values. We identified homozygous relatives, mainly siblings, on the basis of HLA identity with the proband and by HFE genotyping. Disease-related conditions were cirrhosis, hepatic fibrosis, elevated amino-transferase values, and hemochromatotic arthropathy.
We identified 214 homozygous relatives of 291 homozygous probands. Of the 113 men in this group (mean age, 41 years), 96 (85 percent) had iron overload, and 43 (38 percent) had at least one disease-related condition. Of the 52 men over 40 years of age, 27 (52 percent) had at least one disease-related condition. Of the 101 female homozygous relatives (mean age, 44 years), 69 (68 percent) had iron overload, and 10 (10 percent) had at least one disease-related condition. Of the 43 women over 50 years of age, 7 (16 percent) had at least one disease-related condition. If the proband had a disease-related condition, relatives who were men were more likely to have morbidity than if the proband had no disease-related condition.
A substantial number of homozygous relatives of patients with hemochromatosis--more commonly men than women--have conditions related to hemochromatosis that have yet to be detected clinically.
每1000名白人中约有5人患血色素沉着症，该病通常由与HLA连锁的HFE基因突变的纯合性引起。尽管有人提出进行筛查，但与血色素沉着症相关疾病的纯合子比例尚不确定。
我们研究了血色素沉着症先证者亲属中与疾病相关情况的患病率。我们确定了那些因血色素沉着症的体征或症状就诊于诊所或转铁蛋白饱和度值升高的先证者。我们根据与先证者的HLA一致性以及HFE基因分型确定纯合子亲属，主要是兄弟姐妹。与疾病相关的情况包括肝硬化、肝纤维化、转氨酶值升高和血色素沉着性关节病。
我们确定了291名纯合子先证者的214名纯合子亲属。在该组的113名男性（平均年龄41岁）中，96名（85%）有铁过载，43名（38%）至少有一种与疾病相关的情况。在52名40岁以上的男性中，27名（52%）至少有一种与疾病相关的情况。在101名女性纯合子亲属（平均年龄44岁）中，69名（68%）有铁过载，10名（10%）至少有一种与疾病相关的情况。在43名50岁以上的女性中，7名（16%）至少有一种与疾病相关的情况。如果先证者有与疾病相关的情况，男性亲属比先证者没有与疾病相关情况时更易发病。
大量血色素沉着症患者的纯合子亲属——男性比女性更常见——有与血色素沉着症相关但尚未被临床检测到的情况。
