Jacobs E M G, Verbeek A L M, Kreeftenberg H G, van Deursen C Th B M, Marx J J M, Stalenhoef A F H, Swinkels D W, de Vries R A
Department of Clinical Chemistry, University Medical Centre Groningen, Groningen, the Netherlands.
Neth J Med. 2007 Dec;65(11):419-24.
HFE-related hereditary haemochromatosis (HH) is an iron overload disease attributed to the highly prevalent homozygosity for the C282Y mutation in the HFE gene. The pathophysiology of this error in iron metabolism is not completely elucidated yet, although deficiency of the iron regulatory hormone hepcidin appears to play a role. Ways of diagnosing iron overload include measurement of the serum iron parameters, i.e. serum transferrin saturation and serum ferritin, by a liver biopsy or by calculating the amount of mobilisable body iron withdrawn by phlebotomies. Clinical signs attributed to HFE-related HH include liver failure, arthralgia, chronic fatigue, diabetes mellitus and congestive heart failure. organ failure can be prevented by phlebotomies starting before irreversible damage has occurred. Therefore, screening to facilitate early diagnosis is desirable in individuals at risk of developing HFE-related iron overload. over time it appeared that the clinical penetrance of the HFE mutations was much lower than had previously been thought. This changed the opinion about a suitable screening modality from case detection, via population screening, to family screening as the most appropriate method to prevent HFE-related disease. However, before the implementation of family screening it is vital to have thorough information on the relevance of the specific health problem involved, on the clinical penetrance of C282Y homozygosity and on the effectiveness of the screening approach.
与HFE相关的遗传性血色素沉着症（HH）是一种铁过载疾病，归因于HFE基因中C282Y突变的高频率纯合性。尽管铁调节激素铁调素的缺乏似乎起了作用，但这种铁代谢错误的病理生理学尚未完全阐明。诊断铁过载的方法包括测量血清铁参数，即血清转铁蛋白饱和度和血清铁蛋白，通过肝活检或计算通过放血抽取的可动员体内铁的量。与HFE相关的HH的临床体征包括肝衰竭、关节痛、慢性疲劳、糖尿病和充血性心力衰竭。在不可逆转的损伤发生之前开始放血可以预防器官衰竭。因此，对于有发生HFE相关铁过载风险的个体，进行筛查以促进早期诊断是可取的。随着时间的推移，似乎HFE突变的临床外显率比以前认为的要低得多。这改变了关于合适筛查方式的观点，从病例检测、人群筛查，转变为家庭筛查，认为家庭筛查是预防HFE相关疾病的最合适方法。然而，在实施家庭筛查之前，至关重要的是要全面了解所涉及的特定健康问题的相关性、C282Y纯合性的临床外显率以及筛查方法的有效性。
