title: Clinical observations and treatment of pediatric homozygous familial hypercholesterolemia due to a low-density lipoprotein receptor defect.
abstract: BACKGROUND
  Clinical observation and treatment of children with homozygous familial hypercholesterolemia (HoFH) has rarely been reported. We report clinical observations and treatment of 10 ethnic Chinese children with HoFH due to low-density lipoprotein receptor (LDLR) defect.
  
  
  OBJECTIVE
  In children with HoFH, we evaluated the response to conventional cholesterol-lowering drug therapy and performed LDLR gene analysis.
  
  
  METHODS
  A retrospective review of lipid profile changes in pediatric patients diagnosed with HoFH seen in our pediatric endocrinology outpatient clinic was performed. HoFH was diagnosed by molecular study of these patients and their parents.
  
  
  RESULTS
  One novel (c.64del G) and 12 known mutations were found in the LDLR gene. Mutation of p.C308Y was the most common and was found in 26% of the studied alleles.Seven patients had fair responses to conventional drug therapy (high-dose statin with ezetimibe) with a reduction of 50% or more of the total cholesterol levels. The low-density lipoprotein-cholesterol levels of three patients decreased to lower than 160 mg/dL. One who had a good response to conventional drug therapy developed significant atheromatous plaques (largest plaque: 7.4 × 2.7 cm) in the extracranial carotid arteries and myocardial ischemia changes at 11 years old.
  
  
  CONCLUSIONS
  The results suggest that despite aggressive therapy, many patients are not well controlled; atherosclerosis may progress, and novel therapies are required.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, R.O.C; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
authors.forename: Pao-Chin
authors.initials: PC
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Hao-Chuan
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, R.O.C; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Yung-Hsiu
authors.initials: YH
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Jun-Kai
authors.initials: JK
authors.lastname: Huang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. Electronic address: mjcharng@vghtpe.gov.tw.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Charng
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, R.O.C; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. Electronic address: dmniu1111@yahoo.com.tw.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D000069438:Ezetimibe / Q000008:administration & dosage; D005260:Female; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011973:Receptors, LDL; D000069438:Ezetimibe
keywords: Ezetimibe; Homozygous familial hypercholesterolemia; LDL apheresis; LDL receptor; Liver transplantation; Statin; Total cholesterol