Univ Rennes, CHU Rennes, INSERM CIC1414, F-35000, Rennes, France; National Reference Center for Hemochromatosis and iron metabolism disorder, CHU Rennes, F-35000, Rennes, France.
Univ Rennes, CHU Rennes, INSERM CIC1414, F-35000, Rennes, France; National Reference Center for Hemochromatosis and iron metabolism disorder, CHU Rennes, F-35000, Rennes, France.
J Hepatol. 2022 Mar;76(3):568-576. doi: 10.1016/j.jhep.2021.10.022. Epub 2021 Nov 5.
BACKGROUND & AIMS: Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening.
Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation.
Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 μg/L, and liver iron concentration (LIC) 166±77 μmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort 0.83 [0.78-0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77-0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6 (91.7-98.3) %, specificity 49.5 (45.5-53.6) %, positive likelihood ratio 1.8 (1.6-2.0) and negative likelihood ratio 0.17 (0.04-0.37).
We describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice.
Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.
铁蛋白病是一种罕见的遗传性铁过载疾病，可能存在漏诊，最近的数据表明其发病率高于此前的推测。由于费用问题以及缺乏明确的检测标准，大规模的分子筛查无法开展。因此，我们旨在开发一种易于获得的评分系统以促进和加强铁蛋白病的筛查。
本研究的原始队列纳入了 2008 年至 2016 年间在我们的罕见病网络中接受铁蛋白病检测的先证者。前瞻性地记录数据。单变量和多变量逻辑回归用于确定显著标准，并用比值比构建加权评分。使用具有预设 90%敏感性目标的 ROC 曲线定义截断值。使用独立队列进行交叉验证。
本研究的原始队列纳入了 1306 例患者。平均年龄为 55±14 岁，铁蛋白 1351±1357μg/L，肝脏铁浓度（LIC）166±77μmol/g。32 例患者检测到致病性变异。多变量分析显示，女性、年龄较小、铁蛋白水平较高、LIC 较高、无高血压或糖尿病与铁蛋白病的诊断显著相关（整个原始队列的 AUC 为 0.83[0.78-0.88]）。该评分基于性别、年龄、是否存在高血压或糖尿病、铁蛋白水平和 LIC。在无缺失值的原始队列中，AUC 为 0.83（0.77-0.88）。当使用 9.5 作为截断值时，敏感性为 93.6%（91.7%-98.3%），特异性为 49.5%（45.5%-53.6%），阳性似然比为 1.8（1.6-2.0），阴性似然比为 0.17（0.04-0.37）。
我们描述了一种简单、具有良好诊断性能的易于获得的评分，可用于在常规临床实践中筛查铁蛋白病患者。
与代谢综合征相关的铁过载增加是一种非常常见的情况。铁蛋白病是一种显性遗传性铁过载疾病，其发病率高于最初的推测。两者很难区分，但由于遗传检测的可用性有限以及缺乏明确的指导方针，无法进行充分的筛查。我们在此描述了一种简单而明确的临床评分，以帮助临床医生决定是否进行遗传检测。
