Ana Catarina Alves, Rodrigo Alonso, José Luís Diaz-Diaz, Ana Margarida Medeiros, Cinthia E. Jannes, Alonso Merchan, Norma A. Vasques-Cardenas, Ada Cuevas, Ana Paula Chacra, Jose E. Krieger, Raquel Arroyo, Francisco Arrieta, Laura Schreier, Pablo Corral, Virginia G. Bañares, Maria B. Araujo, Paula Bustos, Sylvia Asenjo, Mario Stoll, Nicolás Dell’Oca, Maria Reyes, Andrés Ressia, Rafael Campo, Maria T. Magaña-Torres, Roopa Metha, Carlos A. Aguilar-Salinas, José J. Ceballos-Macias, Álvaro J. Ruiz Morales, Pedro Mata, Mafalda Bourbon, Raul D. Santos

The objective was to characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. 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). 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.
Doi: 10.1161/ATVBAHA.120.313722

Cited as: Alves AC, Alonso R, Diaz-Diaz JL, Medeiros AM, Jannes CE, Merchan A, Vasques-Cardenas NA, Cuevas A, Chacra AP, Krieger JE, Arroyo R, Arrieta F, Schreier L, Corral P, Bañares VG, Araujo MB, Bustos P, Asenjo S, Stoll M, Dell’Oca N, Reyes M, Ressia A, Campo R, Magaña-Torres MT, Metha R, Aguilar-Salinas CA, Ceballos-Macias JJ, Morales ÁJR, Mata P, Bourbon M, Santos RD (2020) Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica. Arterioscler Thromb Vasc Biol. 40(10):2508-2515;