title: Phenotype diversity among patients with homozygous familial hypercholesterolemia: A cohort study.
abstract: OBJECTIVE
  Homozygous familial hypercholesterolaemia (HoFH) is a rare disorder usually caused by mutations in both alleles of the low-density lipoprotein receptor gene (LDLR). Premature death, often before the age of 20 years, was a common fate for patients with HoFH prior to the introduction of statins in 1990 and the use of lipoprotein apheresis. Consequently, HoFH has been widely considered a condition exclusive to a population comprising very young patients with extremely high LDL cholesterol (LDL-C) levels. However, recent epidemiologic and genetic studies have shown that the HoFH patient population is far more diverse in terms of age, LDL-C levels, and genetic aetiology than previously realised. We set out to investigate the clinical characteristics regarding age and LDL-C ranges of patients with HoFH.
  
  
  RESULTS
  We analysed the data from 3 recent international studies comprising a total of 167 HoFH patients. The age of the patients ranged from 1 to 75 years, and a large proportion of the patients, both treated and untreated, exhibited LDL-C levels well below the recommended clinical diagnostic threshold for HoFH. LDL-C levels ranged from 4.4 mmol/L to 27.2 mmol/L (170-1052 mg/dL) for untreated patients, and from 2.6 mmol/L to 20.3 mmol/L (101-785 mg/dL) for treated patients. When patients were stratified according to LDLR functionality, a similarly wide range of age and LDL-C values was observed regardless of LDLR mutation status.
  
  
  CONCLUSIONS
  These results demonstrate that HoFH is not restricted to very young patients or those with extremely high LDL-C levels.
authors.affiliation: Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: frederick.raal@wits.ac.za.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, Netherlands. Electronic address: b.sjouke@amc.uva.nl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sjouke
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, Netherlands. Electronic address: g.k.hovingh@amc.uva.nl.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Medical Affairs, Sanofi Genzyme, 500 Kendall Street, Cambridge, MA 02142, USA. Electronic address: Barton.isaac@sanofi.com.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Isaac
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000235:genetics*; D007223:Infant; D007391:International Cooperation; D008875:Middle Aged; D009154:Mutation; D009841:Oligonucleotides / Q000627:therapeutic use; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics; D012042:Registries; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D009841:Oligonucleotides; D011973:Receptors, LDL; C524142:mipomersen
keywords: Cholesterol; Familial hypercholesterolaemia; Lipoproteins