Fourgeaud Mélanie, Lebreton Louis, Belabbas Khaldia, Di Filippo Mathilde, Rigalleau Vincent, Couffinhal Thierry, Pucheu Yann, Barat Pascal, Ged Cécile, Bérard Annie M
Service de Biochimie, Groupe Hospitalier Pellegrin, CHU de Bordeaux - Place Amélie Raba Léon, F-33000 Bordeaux, France; Université Bordeaux, 146 rue Léo Saignat, F-33076 Bordeaux, France.
Service de Biochimie, Groupe Hospitalier Pellegrin, CHU de Bordeaux - Place Amélie Raba Léon, F-33000 Bordeaux, France.
J Clin Lipidol. 2022 May-Jun;16(3):298-305. doi: 10.1016/j.jacl.2022.03.002. Epub 2022 Mar 17.
Familial hypercholesterolemia (FH) is the most common genetic disorder associated with a high risk for premature atherosclerotic cardiovascular disease attributable to increased levels of LDL-cholesterol (LDL-C) from birth. FH is both underdiagnosed and undertreated.
We describe the clinical, biological, and genetic characteristics of 147 patients in France with clinical FH (including a group of 26 subjects aged < 20 years); we explore how best to detect patients with monogenic FH.
We retrospectively reviewed all available data on patients undergoing genetic tests for FH from 2009 to 2019. FH diagnoses were based on the Dutch Lipid Clinics Network (DLCN) scores of adults, and elevated LDL-C levels in subjects < 20 years of age. We evaluated LDLR, APOB, and PCSK9 status.
The mutations of adults (in 25.6% of all adults) were associated with DLCN scores indicating "possible FH," "probable FH, and "definitive FH" at rates of 4%, 16%, and 53%, respectively. The areas under the ROC curves of the DLCN score and the maximum LDL-C level did not differ (p = 0.32). We found that the pediatric group evidenced more monogenic etiologies (77%, increasing to 91% when an elevated LDL-C level was combined with a family history of hypercholesterolemia and/or premature coronary artery disease).
Diagnosis of monogenic FH may be optimized by screening children in terms of their LDL-C levels, associated with reverse-cascade screening of relatives when the children serve as index cases.
家族性高胆固醇血症（FH）是最常见的遗传性疾病，由于出生时低密度脂蛋白胆固醇（LDL-C）水平升高，导致过早发生动脉粥样硬化性心血管疾病的风险很高。FH的诊断和治疗均不足。
我们描述了法国147例临床诊断为FH的患者（包括一组26名年龄<20岁的受试者）的临床、生物学和遗传特征；我们探讨如何最好地检测单基因FH患者。
我们回顾性分析了2009年至2019年接受FH基因检测患者的所有可用数据。FH诊断基于荷兰脂质诊所网络（DLCN）对成年人的评分，以及<20岁受试者的LDL-C水平升高情况。我们评估了低密度脂蛋白受体（LDLR）、载脂蛋白B（APOB）和前蛋白转化酶枯草溶菌素9（PCSK9）的状态。
成人突变（占所有成人的25.6%）与DLCN评分相关，表明“可能FH”“很可能FH”和“确诊FH”的发生率分别为4%、16%和53%。DLCN评分和最大LDL-C水平的ROC曲线下面积无差异（p = 0.32）。我们发现，儿科组单基因病因更多（77%，当LDL-C水平升高与高胆固醇血症家族史和/或早发冠状动脉疾病相结合时，这一比例增至91%）。
通过筛查儿童的LDL-C水平，并在儿童作为索引病例时对亲属进行反向级联筛查，可能优化单基因FH的诊断。
