Crawford D H, Jazwinska E C, Cullen L M, Powell L W
Clinical Sciences Unit, Queensland Institute of Medical Research and University of Queensland, Brisbane, Australia.
Gastroenterology. 1998 May;114(5):1003-8. doi: 10.1016/s0016-5085(98)70320-8.
BACKGROUND & AIMS: In the absence of a genetic test, diagnostic criteria for hereditary hemochromatosis have been imprecise. The identification of the HFE gene and the C282Y mutation allow definition of expression of this disease and reassessment of diagnostic criteria. The aim of this study was to analyze the concordance between the genetic diagnosis and the previous clinical diagnosis in families with hemochromatosis.
Three hundred subjects were tested for the C282Y mutation and were grouped as homozygous, heterozygous, or homozygous normal.
All adults previously diagnosed as homozygous or heterozygous for HLA-linked hereditary hemochromatosis carried at least one C282Y mutation. Two adolescents, previously thought to be homozygous, had no C282Y mutation. Of 127 subjects homozygous for the mutation, 105 met criteria for diagnosis. Iron overload was not expressed in 6.7% of homozygous men and 32.7% of homozygous women. The iron indices in 8 of 171 subjects heterozygous for the C282Y mutation were within the range previously regarded as indicative of homozygosity. Seven of these 8 carried the H63D mutation.
In Australia, 17.3% of subjects homozygous for the C282Y mutation do not express iron overload to meet current diagnostic criteria of hemochromatosis. In subjects heterozygous for the mutation, 4.8% have iron overload in the range previously diagnosed as homozygous. Nonexpression is common, particularly in women.
在缺乏基因检测的情况下，遗传性血色素沉着症的诊断标准一直不够精确。HFE基因和C282Y突变的鉴定使得能够定义这种疾病的表现形式并重新评估诊断标准。本研究的目的是分析血色素沉着症家族中基因诊断与先前临床诊断之间的一致性。
对300名受试者进行C282Y突变检测，并分为纯合子、杂合子或纯合正常组。
所有先前被诊断为HLA连锁遗传性血色素沉着症纯合子或杂合子的成年人至少携带一个C282Y突变。两名先前被认为是纯合子的青少年没有C282Y突变。在127名该突变纯合子受试者中，105名符合诊断标准。6.7%的纯合子男性和32.7%的纯合子女性未表现出铁过载。在171名C282Y突变杂合子受试者中，有8人的铁指标在先前被认为指示纯合性的范围内。这8人中有7人携带H63D突变。
在澳大利亚，17.3%的C282Y突变纯合子受试者未表现出铁过载以符合目前血色素沉着症的诊断标准。在该突变杂合子受试者中，4.8%的人铁过载处于先前诊断为纯合子的范围内。无表现情况很常见，尤其是在女性中。
