Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica

• Main Author: Alves, Ana Catarina
• Publication Date: 2020
• Other Authors: Alonso, Rodrigo, Diaz-Diaz, José Luís, Medeiros, Ana Margarida, Jannes, Cinthia E., Merchan, Alonso, Vasques-Cardenas, Norma A., Cuevas, Ada, Chacra, Ana Paula, Krieger, Jose E., Arroyo, Raquel, Arrieta, Francisco, Schreier, Laura, Corral, Pablo, Bañares, Virginia G., Araujo, Maria B., Bustos, Paula, Asenjo, Sylvia, Stoll, Mario, Dell'Oca, Nicolás, Reyes, Maria, Ressia, Andrés, Campo, Rafael, Magaña-Torres, Maria T, Metha, Roopa, Aguilar-Salinas, Carlos A, Ceballos-Macias, José J, Morales, Álvaro J Ruiz, Mata, Pedro, Bourbon, Mafalda, Santos, Raul D
• Format: Article
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10400.18/7220
• topic: Atherosclerosis; Cardiovascular Disease; Cholesterol; Hypercholesterolemia; Phenotype; Familial Hypercholesterolemia; Iberoamerica; Doenças Cardio e Cérebro-vasculares

Objective: 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 LDLR. True HoFH due to LDLR variants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=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 LDLR variants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of LDLR variant. From 118 subjects with LDLR variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 LDLR variants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). Conclusions: 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.