Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, 20133, Italy; IRCCS MultiMedica, Sesto San Giovanni, Milan, 20099, Italy.
Fondazione SISA (Società Italiana per lo Studio dell'Aterosclerosi), 20133, Milano, Italy.
Atherosclerosis. 2023 Nov;385:117231. doi: 10.1016/j.atherosclerosis.2023.117231. Epub 2023 Aug 12.
We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.
From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.
The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.
In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age.
本研究旨在描述基于家族性高胆固醇血症（FH）典型特征（如胆固醇蓄积的身体征象和个人或家族的早发心血管疾病或高胆固醇血症病史）进行儿童 FH 诊断的局限性，并比较其在成年和儿科 FH 人群中的患病率，同时举例说明如何通过收集更多信息来更有效地在年轻时诊断 FH。
我们从意大利 LIPIGEN 队列中选择了 1188 名（≥18 岁）和 708 名（<18 岁）经基因证实的杂合子 FH 患者，且无缺失的个人 FH 特征。比较了两组患者的个人和家族 FH 特征的患病率。对于儿科队列的一个亚组（N=374），还将二级亲属中早发冠心病（CHD）的数据纳入评估。
与成年患者相比，儿童/青少年 FH 患者中典型 FH 特征的患病率较低：肌腱黄色瘤分别为 2.1%和 13.1%，角膜弓分别为 1.6%和 11.2%。与成年患者相比，儿童/青少年中无早发 CHD 或脑/外周血管疾病的临床病史，分别为 8.8%和 5.6%。一级亲属中早发 CHD 的患病率在成年患者中明显高于儿童/青少年（38.9%比 19.7%）。在亚组分析中，374 名患者中有 63 名（16.8%）报告了父母的早发 CHD 事件，但如果将评估范围扩大到二级亲属，这一比例增加到 54.0%。
在儿童中，典型 FH 特征明显不如成年患者那么具有信息量。通过更全面的数据收集，增加关于二级亲属的信息，可以提高在年轻时诊断 FH 的能力。
