title: Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society.
abstract: OBJECTIVE
  Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.
  
  
  RESULTS
  Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.
  
  
  CONCLUSIONS
  This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA mcuchel@mail.med.upenn.edu.
authors: Marina
authors: M
authors: Cuchel
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Eric
authors: E
authors: Bruckert
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Henry N
authors: HN
authors: Ginsberg
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Frederick J
authors: FJ
authors: Raal
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Raul D
authors: RD
authors: Santos
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Robert A
authors: RA
authors: Hegele
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Jan Albert
authors: JA
authors: Kuivenhoven
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Børge G
authors: BG
authors: Nordestgaard
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Olivier S
authors: OS
authors: Descamps
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Elisabeth
authors: E
authors: Steinhagen-Thiessen
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Anne
authors: A
authors: Tybjærg-Hansen
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Gerald F
authors: GF
authors: Watts
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Maurizio
authors: M
authors: Averna
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Catherine
authors: C
authors: Boileau
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Jan
authors: J
authors: Borén
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Alberico L
authors: AL
authors: Catapano
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Joep C
authors: JC
authors: Defesche
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: G Kees
authors: GK
authors: Hovingh
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Steve E
authors: SE
authors: Humphries
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Petri T
authors: PT
authors: Kovanen
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Luis
authors: L
authors: Masana
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Päivi
authors: P
authors: Pajukanta
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Klaus G
authors: KG
authors: Parhofer
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Kausik K
authors: KK
authors: Ray
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Anton F H
authors: AF
authors: Stalenhoef
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Erik
authors: E
authors: Stroes
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Marja-Riitta
authors: MR
authors: Taskinen
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Albert
authors: A
authors: Wiegman
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: Olov
authors: O
authors: Wiklund
authors: Institute for Translational Medicine and Therapeutics, University of Pennsylvania, 8039 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors: M John
authors: MJ
authors: Chapman
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001112:Arcus Senilis / Q000209:etiology; D050197:Atherosclerosis / Q000175:diagnosis; D001781:Blood Component Removal / Q000379:methods; D002318:Cardiovascular Diseases / Q000209:etiology; D008078:Cholesterol, LDL / Q000378:metabolism; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005787:Gene Frequency / Q000235:genetics; D018740:Genetic Heterogeneity; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D016031:Liver Transplantation / Q000379:methods; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D017410:Practice Guidelines as Topic; D014973:Xanthomatosis / Q000209:etiology
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL
keywords: Diagnosis; Ezetimibe; Genetics; Homozygous familial hypercholesterolaemia; Lipoprotein apheresis; Lomitapide; Mipomersen; Phenotypic heterogeneity; Statins