Gleeson F, Ryan E, Barrett S, Crowe J
Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin, Ireland.
Eur J Gastroenterol Hepatol. 2004 Sep;16(9):859-63. doi: 10.1097/00042737-200409000-00008.
In Ireland, the homozygote frequency of the C282Y mutation in the HFE gene is 1/83. The biochemical expression of this mutation is high in haemochromatosis (HH) individuals identified through family screening, but the clinical expression of the mutation in Irish HH subjects to date has not been investigated fully.
To determine the clinical, biochemical and histological penetrance of the C282Y mutation in Irish C282Y homozygotes identified through family screening.
Two hundred and nine C282Y homozygous individuals comprising of 172 first-degree relatives, 31 second-degree relatives and four unrelated individuals were identified following HFE mutation analysis of 167 families. The following variables were analysed: age at identification, gender, fasting transferrin saturation, fasting serum ferritin, liver enzymes, clinical symptomatology, liver histopathology and histochemical iron staining.
An elevated transferrin saturation in combination with an elevated ferritin was present in 43.4% of males and 23.3% of females. Abnormal liver enzymes were found in 32.3% of males. Diabetes, a haemochromatosis-specific association, was noted in 2.8% of males. Of those individuals requiring liver histopathology evaluation, 38% had moderate-to-severe iron staining, and 42% had fibrosis; 2.8% of the biopsied cohort had cirrhosis. Thus, HH cirrhotics were identified in less than 1% of the screened population.
Although the homozygote frequency in Ireland is very high, the prevalence of advanced liver disease was less than 1% of the family members screened. Nevertheless, 42% of biopsied patients had histological evidence of iron overload-related architectural change and 2.8% had cirrhosis. This cohort of young people had previously unrecognized biochemical iron overload and histopathological change. This emphasizes the importance and value of both genetic and biochemical screening in first-degree relatives of identified homozygotes.
在爱尔兰，HFE基因中C282Y突变的纯合子频率为1/83。通过家族筛查确定的血色素沉着症（HH）个体中，这种突变的生化表现较高，但迄今为止，爱尔兰HH受试者中该突变的临床表型尚未得到充分研究。
确定通过家族筛查鉴定出的爱尔兰C282Y纯合子中C282Y突变的临床、生化和组织学外显率。
对167个家庭进行HFE突变分析后，确定了209名C282Y纯合个体，其中包括172名一级亲属、31名二级亲属和4名无血缘关系的个体。分析了以下变量：确诊年龄、性别、空腹转铁蛋白饱和度、空腹血清铁蛋白、肝酶、临床症状、肝脏组织病理学和组织化学铁染色。
43.4%的男性和23.3%的女性存在转铁蛋白饱和度升高和铁蛋白升高的情况。32.3%的男性发现肝酶异常。2.8%的男性患有糖尿病，这是一种血色素沉着症特异性关联疾病。在需要进行肝脏组织病理学评估的个体中，38%有中度至重度铁染色，42%有纤维化；2.8%的活检队列患有肝硬化。因此，在筛查人群中，HH肝硬化患者不到1%。
尽管爱尔兰的纯合子频率很高，但晚期肝病的患病率在筛查的家庭成员中不到1%。然而，42%的活检患者有铁过载相关结构改变的组织学证据，2.8%患有肝硬化。这群年轻人之前存在未被识别的生化铁过载和组织病理学改变。这强调了对已鉴定纯合子的一级亲属进行基因和生化筛查的重要性和价值。
