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

Autor:	Alves AC; 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.).; Faculdade de Ciências, Universidade de Lisboa, BioISI-Biosystems & Integrative Sciences Institute, Portugal (A.C.A., A.M.M., M.B.)., Alonso R; Center for Advanced Metabolic Medicine and Nutrition, Santiago, Chile (R. Alonso, A.C.).; Fundación Hipercolesterolemia Familiar, Madrid, Spain (R. Alonso, R. Arroyo, P.M.)., Diaz-Diaz JL; Department of Internal Medicine. Hospital Universitario A Coruña, Spain (J.L.D.-D.)., Medeiros AM; 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.).; Faculdade de Ciências, Universidade de Lisboa, BioISI-Biosystems & Integrative Sciences Institute, Portugal (A.C.A., A.M.M., M.B.)., Jannes CE; Heart Institute (InCor) University of São Paulo Medical School Hospital São Paulo, Brazil (C.E.J., A.P.C., J.E.K., R.D.S.)., Merchan A; Fundacion Clinica SHAIO, Cardiologia, Bogota, Colombia (A.M.)., Vasques-Cardenas NA; Universidad Autonoma de Guadalajara, Facultad de Medicina Zapopan, Mexico (N.A.V.-C.)., Cuevas A; Center for Advanced Metabolic Medicine and Nutrition, Santiago, Chile (R. Alonso, A.C.)., Chacra AP; Heart Institute (InCor) University of São Paulo Medical School Hospital São Paulo, Brazil (C.E.J., A.P.C., J.E.K., R.D.S.)., Krieger JE; Heart Institute (InCor) University of São Paulo Medical School Hospital São Paulo, Brazil (C.E.J., A.P.C., J.E.K., R.D.S.)., Arroyo R; Fundación Hipercolesterolemia Familiar, Madrid, Spain (R. Alonso, R. Arroyo, P.M.)., Arrieta F; Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain (F.A.)., Schreier L; Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Argentina (L.S.)., Corral P; Universidad FASTA, Facultad de Medicina, Cátedra Farmacología e Investigación, Mar del Plata, Argentina (P.C.)., Bañares VG; Administracion Nacional de Laboratorios e Institutos de Salud 'Dr Carlos G. Malbrán'', Centro Nacional de Genética Médica, Departamento de Genética Experimental, Buenos Aires, Argentina (V.G.B.)., Araujo MB; Hospital Nacional de Pediatria ¨Dr JP Garraham¨, Servicio de Nutrición, Buenos Aires, Argentina (M.B.A.)., Bustos P; Facultad de Farmacia (P.B.), Universidad de Concepción, Chile., Asenjo S; Facultad de Medicina (S.A.), Universidad de Concepción, Chile., Stoll M; Comision Honoraria de Salud Cardiovascular, Programa GENYCO, Laboratorio de Genética Molecular, Montevideo, Uruguay (M.S., N.D., X.R., A.R.)., Dell'Oca N; Comision Honoraria de Salud Cardiovascular, Programa GENYCO, Laboratorio de Genética Molecular, Montevideo, Uruguay (M.S., N.D., X.R., A.R.)., Reyes M; Fundación Cardiovascular de Colombia, Cardiologia, Bogotá (R.C.)., Ressia A; Comision Honoraria de Salud Cardiovascular, Programa GENYCO, Laboratorio de Genética Molecular, Montevideo, Uruguay (M.S., N.D., X.R., A.R.)., Campo R; Fundación Cardiovascular de Colombia, Cardiologia, Bogotá (R.C.)., Magaña-Torres MT; Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica del Occidente, Guadalajara, México (M.T.M.-T.)., Metha R; Unidad de Investigación de Enfermedades Metabólicas (R.M., C.A.A.S.)., Aguilar-Salinas CA; Unidad de Investigación de Enfermedades Metabólicas (R.M., C.A.A.S.)., Ceballos-Macias JJ; Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México. Servicio de Endocrinología, Unidad de Especialidades Médicas, Secretaría de la Defensa Nacional, Mexico (J.J.C.-M.)., Morales ÁJR; Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Javerina, Bogotá, Colombia (A.J.R.)., Mata P; Fundación Hipercolesterolemia Familiar, Madrid, Spain (R. Alonso, R. Arroyo, P.M.)., Bourbon M; 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.).; Faculdade de Ciências, Universidade de Lisboa, BioISI-Biosystems & Integrative Sciences Institute, Portugal (A.C.A., A.M.M., M.B.)., Santos RD; Heart Institute (InCor) University of São Paulo Medical School Hospital São Paulo, Brazil (C.E.J., A.P.C., J.E.K., R.D.S.).; Hospital Israelita Albert Einstein, Sao Paulo, Brazil (R.D.S.).
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2020 Oct; Vol. 40 (10), pp. 2508-2515. Date of Electronic Publication: 2020 Aug 06.
DOI:	10.1161/ATVBAHA.120.313722
Abstrakt:	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.
Databáze:	MEDLINE
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