遗传性血色病总论.pptVIP

遗传性血色病 Hereditary Hemochromatosis 马 雄 上海第二医科大学附属仁济医院 上 海 市 消 化 疾 病 研 究 所 概 述 HH是常染色体隐性遗传疾病，是白种人群中最常见遗传性疾病的一种。 它是一种由于铁代谢紊乱引起体内铁在组织中进行性沉积的先天性代谢障碍性疾病。 国内只有零星报道，90年以前的文献报道有15例，上海曾报道一血色病家族。 HFE基因 HFE蛋白与转铁蛋白受体1（ TfR1）相关，调控体内铁负荷； 有两种基因变异：C282Y，H63D C282Y纯合子，C282Y-H63D复合性杂合子； 临床表现（三联征） 色素沉着 肝肿大 糖尿病 筛选的推荐 在拟似铁超负荷患者和HH所有1，2级亲属中快速检测转铁蛋白饱和度(TS) 铁蛋白增加了诊断的精确性； TS也是普通人群筛查的首选。 HH的处理目的 早期诊断以防止组织内铁沉积导致的器官损伤和功能衰竭； 筛查和早期鉴定无症状HH病例以减少死亡率； 识别和诊断有症状HH病例，以减缓进展和并发症； 充分治疗以促进快速、安全、有效地祛除铁； 严密随访，维持治疗。 治 疗 每周一次或两次放血500ml； 在每次放血之前检查血细胞比容，允许血细胞比容较以前水平下降不到20%； 每10-20次放血检测一次血清铁蛋白； 血清铁蛋白低于50 ng/ml，停止频繁放血； 维持放血保持血清铁蛋白25-50ng/ml； 避免维生素C的补充。 原位肝移植术 当诊断和治疗延误，患者已经发展到肝脏疾病的终末期时则需要进行原位肝移植术。 进行肝移植的死亡率比其他原因所致终末期肝病而进行肝移植的死亡率高。 移植后死亡原因常见为感染和心脏并发症。 谢 谢！ Figure 8-1. History of hemochromatosis. Trousseau was the first to describe a case of hemochromatosis in the French pathology literature in 1865 [1]. In 1889, von Recklinghausen in the German literature, coined the term hemochromatosis, thinking that it was a blood disorder that caused pigmentation [1]. However, it was not until 1935 that Sir Wilfred Sheldon, a British gerontologist, published a monograph describing all 311 cases of the disease that were reported in the world s literature to that point, including several from his own records [1]. He concluded that hemochromatosis was an inborn error of iron metabolism and that all of the pathologic manifestations were caused by increased iron deposition. Davis and Arrowsmith [2] performed the first liver biopsy on a patient with hemochromatosis and then treated the individual with aggressive phlebotomy. In the 1960s, a controversy developed when MacDonald [3] questioned the inherited nature of the disease, thinking instead that it was related to nutritional changes often associated with alcoholism. The benefits of phlebotomy were first shown by Williams et al. [4] in 1969 and were later confirmed by Niederau et al. [5] in 1985. The benefits of early diagnosis were also demonstrated in 1985 [5].