RT Journal Article T1 Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship A1 Sanchez-Hernandez, Rosa M. A1 Civeira, Fernando A1 Stef, Marianne A1 Perez-Calahorra, Sofia A1 Almagro, Fatima A1 Plana, Nuria A1 Novoa, Francisco J. A1 Saenz-Aranzubia, Pedro A1 Mosquera, Daniel A1 Soler, Cristina A1 Fuentes, Francisco J. A1 Brito-Casillas, Yeray A1 Real, Jose T. A1 Blanco-Vaca, Francisco A1 Ascaso, Juan F. A1 Pocovi, Miguel K1 Alleles K1 Hypercholesterolemia K1 Lipids K1 Mutation K1 Registries AB Background-Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain.Methods and Results-Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH-of whom, 47 were true homozygous (1 for APOB, 5 for LDLRAP1, and 41 for LDLR), 45 compound heterozygous for LDLR, 3 double heterozygous for LDLR and PSCK9, and 2 double heterozygous for LDLR and APOB. No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1: 450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events.Conclusions-HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy. PB Lippincott Williams & Wilkins SN 1942-325X YR 2016 FD 2016-09-28 LK http://hdl.handle.net/10668/19085 UL http://hdl.handle.net/10668/19085 LA en NO Sánchez-Hernández RM, Civeira F, Stef M, Perez-Calahorra S, Almagro F, Plana N, et al. Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship. Circ Cardiovasc Genet. 2016 Dec;9(6):504-510 DS RISalud RD Apr 12, 2025