RT Book, Section
A1 Fisher, Edward A.
A1 Schwartzbard, Arthur Z.
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102698948
T1 Familial Hypercholesterolemia
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessmedicine.mhmedical.com/content.aspx?aid=1102698948
RD 2024/04/20
AB Disease  summary:Familial  hypercholesterolemia  (FH)  is  an  autosomal  dominant,  monogenic  disorder  of  lipoprotein  metabolism  characterized  by  strikingly  elevated  low-density  lipoprotein-cholesterol  (LDL-C),  the  presence  of  xanthomas,  and  premature  atherosclerosis.FH  is  most  often  caused  by  a  defect  in  the  gene  that  encodes  for  the  apolipoprotein  B  or  E  (ApoB  or  E)  (LDL)  receptor  (LDLR).  Over  1000  different  mutations  of  this  receptor  have  been  identified  since  it  was  first  discovered  by  Goldstein  and  Brown  in  the  late  1970s.Impairment  in,  or  in  severe  cases,  a  complete  absence  of  function  of,  LDLR  results  in  reduced  clearance  of  LDL  particles  from  the  circulation  into  many  cell  types.  Because  over  60%  of  total  body  LDLR  is  in  the  liver,  decreased  clearance  of  LDL  particles  by  this  organ  has  a  particularly  potent  effect  on  plasma  LDL-C  levels.  Hypercholesterolemia  is  present  from  birth.  LDL  particles  begin  to  be  retained  in  arterial  sites  early  on  in  life  and  their  uptake  by  macrophages  turn  them  into  foam  cells,  the  fundamental  building  block  of  an  atherosclerotic  plaque.The  FH  homozygote  frequency  is  estimated  to  be  1:1,000,000  worldwide  compared  with  the  heterozygote  frequency  of  1:500.