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

• Autores: Alves, Ana Catarina; 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; 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; Ruiz Morales, Álvaro J; Mata, Pedro; Bourbon, Mafalda; Santos, Raul D
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Arteriosclerosis, Thrombosis, and Vascular Biology 2020;40(10):2508-2515
• Materia: Aterosclerosis; Enfermedad Coronaria; Colesterol; Hipercolesterolemia; Fenotipo
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Alves, Ana Catarina. Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa; Portugal.
Fil: Alonso, Rodrigo. Center for Advanced Metabolic Medicine and Nutrition, Santiago; Chile.
Fil: Diaz-Diaz, José Luís. Hospital Universitario A Coruña. Department of Internal Medicine; España.
Fil: Medeiros, Ana Margarida. Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa; Portugal.
Fil: Jannes, Cinthia E. University of São Paulo. Medical School. Hospital São Paulo. Heart Institute (InCor); Brasil.
Fil: Merchan, Alonso. Fundación Clinica SHAIO, Cardiología, Bogotá; Colombia.
Fil: Vasques-Cardenas, Norma A. Universidad Autónoma de Guadalajara. Facultad de Medicina Zapopan; México.
Fil: Cuevas, Ada. Center for Advanced Metabolic Medicine and Nutrition, Santiago; Chile.
Fil: Chacra, Ana Paula. University of São Paulo. Medical School. Hospital São Paulo. Heart Institute (InCor); Brasil.
Fil: Krieger, Jose E. University of São Paulo. Medical School. Hospital São Paulo. Heart Institute (InCor); Brasil.
Fil: Arroyo, Raquel. Fundación Hipercolesterolemia Familiar, Madrid; España.
Fil: Arrieta, Francisco. Hospital Ramón y Cajal. Departamento de Endocrinología, Madrid; España.
Fil: Schreier, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis; Argentina.
Fil: Corral, Pablo. Universidad FASTA. Facultad de Medicina. Cátedra Farmacología e Investigación, Mar del Plata; Argentina.
Fil: Bañares, Virginia. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica. Departamento de Genética Experimental; Argentina.
Fil: Araujo, Maria B. Hospital Garrahan. Servicio de Nutrición; Argentina.
Fil: Bustos, Paula. Universidad de Concepción. Facultad de Farmacia; Chile.
Fil: Asenjo, Sylvia. Universidad de Concepción. Facultad de Medicina; Chile.
Fil: Stoll, Mario. Programa GENYCO, Laboratorio de Genética Molecular. Comisión Honoraria de Salud Cardiovascular, Montevideo; Uruguay.
Fil: Dell'Oca, Nicolás. Programa GENYCO, Laboratorio de Genética Molecular. Comisión Honoraria de Salud Cardiovascular, Montevideo; Uruguay.
Fil: Reyes, Maria. Fundación Cardiovascular de Colombia. Cardiología; Bogotá.
Fil: Ressia, Andrés. Fundación Cardiovascular de Colombia. Cardiología; Bogotá.
Fil: Campo, Rafael. Instituto Mexicano del Seguro Social. Centro de Investigación Biomédica del Occidente, Guadalajara; México.
Fil: Magaña-Torres, Maria T. Instituto Nacional de Ciencias Médicas y Nutrición. Unidad de Investigación de Enfermedades Metabólicas; México.
Fil: Metha, Roopa. Instituto Nacional de Ciencias Médicas y Nutrición. Unidad de Investigación de Enfermedades Metabólicas; México.
Fil: Aguilar-Salinas, Carlos A. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Departamento de Endocrinología y Metabolismo. Secretaría de la Defensa Nacional. Unidad de Especialidades Médicas. Servicio de Endocrinología; México.
Fil: Ceballos-Macias, José J. Pontificia Universidad Javerina. Facultad de Medicina. Departamento de Medicina Interna, Bogotá; Colombia.
Fil: Ruiz Morales, Álvaro J. Pontificia Universidad Javerina. Facultad de Medicina. Departamento de Medicina Interna, Bogotá; Colombia.
Fil: Mata, Pedro. Fundación Hipercolesterolemia Familiar, Madrid; España.
Fil: Bourbon, Mafalda. Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa; Portugal.
Fil: Santos, Raul D. University of São Paulo. Medical School. Hospital São Paulo. Heart Institute (InCor); Brasil.
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.