Clinical expression of haemochromatosis in Irish C282Y homozygotes identified through family screening
Clinical expression of haemochromatosis in Irish C282Y homozygotes identified through family screening
复制标题
DOI：
10.1097/00042737-200409000-00008
复制
发表时间：
2004-09-01
影响因子：
2.1
通讯作者：
Crowe, J
中科院分区：
文献类型：
--
作者：
Gleeson, F;Ryan, E;Crowe, J
背景在爱尔兰，HFE基因C282 Y突变的纯合子频率为1/83。该突变的生化表达在通过家族筛查鉴定的血色病（HH）个体中是高的，但是迄今为止尚未充分研究爱尔兰HH受试者中该突变的临床表达。通过家系筛查确定爱尔兰C282 Y纯合子中C282 Y突变的生化和组织学特征包括172名一级亲属，31名二级亲属和4名无关个体。以下变量进行了分析：年龄在识别，性别，空腹转铁蛋白饱和度，空腹血清铁蛋白，肝酶，临床病理学，肝组织病理学和组织化学铁staining.Results结合铁蛋白升高的转铁蛋白饱和度升高是存在于43.4%的男性和23.3%的女性。32.3%的男性发现肝酶异常。糖尿病是一种血色病特异性相关疾病，在2.8%的男性中观察到。在需要进行肝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%的活检队列有肝硬化。因此，筛查人群中HH肝硬化的患病率不到1%。结论尽管爱尔兰的纯合子频率非常高，但晚期肝脏疾病的患病率不到筛查家庭成员的1%。然而，42%的活检患者有铁过载相关的结构变化的组织学证据，2.8%有肝硬化。这组年轻人以前未被识别的生化铁过载和组织病理学变化。这强调了遗传和生化筛选的重要性和价值，在一级亲属的确定纯合子。
Background 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.Objectives To determine the clinical, biochemical and histological penetrance of the C282Y mutation in Irish C282Y homozygotes identified through family screening.Method 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.Results 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.Conclusion 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.