title: Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: Insights from SAFEHEART registry.
abstract: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals.
  
  
  
  To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression.
  
  
  
  SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed.
  
  
  
  Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P < .0001), more aortic valve stenosis (P < .05), and lower age at first cardiovascular event (P < .05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant.
  
  
  
  HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.
authors: Fundación Hipercolesterolemia Familiar, Madrid, Spain; Department of Nutrition, Clínica Las Condes, Santiago de Chile, Chile. Electronic address: rodrigoalonsok@gmail.com.
authors: Rodrigo
authors: R
authors: Alonso
authors: Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain.
authors: Jose Luis
authors: JL
authors: Díaz-Díaz
authors: Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain.
authors: Francisco
authors: F
authors: Arrieta
authors: Department of Internal Medicine, IMIBIC, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.
authors: Francisco
authors: F
authors: Fuentes-Jiménez
authors: Department of Internal Medicine, Fundación Jiménez Díaz, Madrid, Spain.
authors: Raimundo
authors: R
authors: de Andrés
authors: Department of Internal Medicine, Hospital de Mérida, Mérida, Spain.
authors: Pedro
authors: P
authors: Saenz
authors: Department of Pediatric Nephrology, Hospital Vall d'Hebrón, Barcelona, Spain.
authors: Gema
authors: G
authors: Ariceta
authors: Department of Endocrinology, Hospital Universitario de Lugo, Lugo, Spain.
authors: José I
authors: JI
authors: Vidal-Pardo
authors: Department of Internal Medicine, Hospital Donostia, San Sebastian, Spain.
authors: Fatima
authors: F
authors: Almagro
authors: Department of Endocrinology, Hospital Universitario de Lugo, Lugo, Spain.
authors: Rosa
authors: R
authors: Argueso
authors: Department of Pediatrics, Hospital Universitario, Salamanca, Spain.
authors: Pablo
authors: P
authors: Prieto-Matos
authors: Department of Internal Medicine, Hospital Universitario, Salamanca, Spain.
authors: José P
authors: JP
authors: Miramontes
authors: Department of Internal Medicine, Hospital de Bellvitge, Barcelona, Spain.
authors: Xavier
authors: X
authors: Pintó
authors: Fundación Hipercolesterolemia Familiar, Madrid, Spain.
authors: Johana
authors: J
authors: Rodriguez-Urrego
authors: Fundación Hipercolesterolemia Familiar, Madrid, Spain; Cardiology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors: Leopoldo
authors: L
authors: Perez de Isla
authors: Fundación Hipercolesterolemia Familiar, Madrid, Spain. Electronic address: pmata@colesterolfamiliar.org.
authors: Pedro
authors: P
authors: Mata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007223:Infant; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics; D012042:Registries / Q000706:statistics & numerical data*; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D011973:Receptors, LDL
keywords: Aortic valve stenosis; Coronary artery disease; Genetic; Homozygous familial hypercholesterolemia; LDL apheresis