Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal (A.C.A., A.M.M., M.B.).
Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Unidade de I&D, Grupo de Investigação Cardiovascular, Lisboa, Portugal (A.C.A., A.M.M., M.B.).
Arterioscler Thromb Vasc Biol. 2020 Oct;40(10):2508-2515. doi: 10.1161/ATVBAHA.120.313722. Epub 2020 Aug 6.
Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the . True HoFH due to variants had higher total (=0.015) and LDL (low-density lipoprotein)-cholesterol (=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (=0.051) and had a greater frequency of xanthomas (=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with variants. Children who are true HoFH had higher frequency of major cardiovascular events (=0.02), coronary heart (=0.013), and aortic/supra-aortic valve diseases (=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of variant. From 118 subjects with variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 variants, those with at least one null allele were younger (=0.003) and had a greater frequency of major cardiovascular events (=0.038) occurring at an earlier age (=0.001).
There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.
描述伊比利亚美洲的纯合家族性高胆固醇血症（HoFH）个体。
在一项横断面回顾性评估中，研究了 134 名具有 HoFH 表型的个体，其中 71 名成年人（年龄 39.3±15.8 岁，38.0%为男性）和 63 名儿童（年龄 8.8±4.0 岁，50.8%为男性）。129 名（96%）可进行基因特征分析。大多数（91%）为纯合子（真 HoFH，n=79，43.0%为儿童，46.8%为男性）或复合杂合子（杂合子家族性高胆固醇血症，n=39，51.3%为儿童，46.2%为男性），携带. 种变异的真 HoFH 总胆固醇（=0.015）和 LDL 胆固醇（=0.008）更高。与复合杂合子家族性高胆固醇血症相比，患有真 HoFH（n=34）的儿童倾向于更早被诊断（=0.051），且黄色瘤的发生率更高（=0.016）。52 名儿童中有 25 名（48%）（2 例缺失信息）和 64 名成年人中有 43 名（67%）（携带 种变异）发生过重大心血管事件。患有真 HoFH 的儿童发生重大心血管事件（=0.02）、冠心病（=0.013）和主动脉/升主动脉瓣疾病（=0.022）的频率高于复合杂合子家族性高胆固醇血症。在成年人中，根据 种变异类型，重大心血管事件无差异。在 118 名携带 种变异的受试者中，76 名（64%）携带 2 种可能致病或致病性变异。在 89 名携带 2 种变异的受试者中，至少有一种缺失等位基因的患者更年轻（=0.003），且更早发生重大心血管事件（=0.038）。
即使在儿童中，心血管疾病的发生率也很高。表型和心血管并发症具有异质性，与分子缺陷类型相关。
