Scotet Virginie, Le Gac Gérald, Mérour Marie-Christine, Mercier Anne-Yvonne, Chanu Brigitte, Ka Chandran, Mura Catherine, Nousbaum Jean-Baptiste, Férec Claude
INSERM U 613 Génétique Moléculaire et Génétique Epidémiologique, Brest, France.
BMC Med Genet. 2005 Jun 1;6:24. doi: 10.1186/1471-2350-6-24.
Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations. The discovery of a candidate gene in 1996 (HFE), and of its main mutation (C282Y), has radically altered the way to diagnose this disease. The aim of this study was to assess the impact of the HFE gene discovery on the clinical presentation and epidemiology of HH.
We studied our cohort of 415 patients homozygous for the C282Y allele and included in a phlebotomy program in a blood centre in western Brittany, France.
In this cohort, 56.9% of the patients were male and 21.9% began their phlebotomy program before the implementation of the genetic test. A significant decrease in the sex ratio was noticed following implementation of this DNA test, from 3.79 to 1.03 (p < 10(-5)), meaning that the proportion of diagnosed females relatives to males greatly increased. The profile of HH patients at diagnosis changed after the DNA test became available. Serum ferritin and iron values were lower and there was a reduced frequency of clinical signs displayed at diagnosis, particularly skin pigmentation (20.1 vs. 40.4%, OR = 0.37, p < 0.001) and hepatomegaly (11.0 vs. 22.7%, OR = 0.42, p = 0.006). In contrast, fatigue became a more common symptom at diagnosis (68.0 vs. 51.2%, OR = 2.03, p = 0.004).
This study highlights the importance of the HFE gene discovery, which has simplified the diagnosis of HH and modified its clinical presentation and epidemiology. This study precisely measures these changes. Enhanced diagnosis of HFE-related HH at an early stage and implementation of phlebotomy treatment are anticipated to maintain normal life expectancy for these patients.
遗传性血色素沉着症（HH）是北欧人群中常见的遗传性铁代谢紊乱疾病。1996年发现了一个候选基因（HFE）及其主要突变（C282Y），这从根本上改变了该疾病的诊断方式。本研究的目的是评估HFE基因发现对HH临床表现和流行病学的影响。
我们研究了法国布列塔尼西部一个血液中心纳入放血治疗项目的415例C282Y等位基因纯合患者队列。
在这个队列中，56.9%的患者为男性，21.9%的患者在基因检测实施之前就开始了放血治疗项目。实施该DNA检测后，性别比显著下降，从3.79降至1.03（p < 10(-5)），这意味着诊断出的女性亲属与男性亲属的比例大幅增加。DNA检测可用后，HH患者的诊断特征发生了变化。血清铁蛋白和铁值较低，诊断时显示的临床体征频率降低，特别是皮肤色素沉着（20.1%对40.4%，OR = 0.37，p < 0.001）和肝肿大（11.0%对22.7%，OR = 0.42，p = 0.006）。相比之下，疲劳在诊断时成为更常见的症状（68.0%对51.2%，OR = 2.03，p = 0.004）。
本研究强调了HFE基因发现的重要性，它简化了HH的诊断，并改变了其临床表现和流行病学。本研究精确测量了这些变化。预计早期加强对HFE相关HH的诊断并实施放血治疗可维持这些患者的正常预期寿命。
