TY  - CHAP
M1  - Book, Section
TI  - Lecithin Cholesterol Acyltransferase Deficiency and Fish Eye Disease
A1  - Santamarina-Fojo, Silvia
A1  - Hoeg†, Jeffrey M.
A1  - Assmann, Gerd
A1  - Bryan Brewer, H.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.147
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Lecithin  cholesterol  acyltransferase  (LCAT)  is  a  plasma  enzyme  that  esterifies  free  cholesterol  present  in  circulating  plasma  lipoproteins.LCAT  deficiency  leads  to  the  development  of  two  clinically  distinct  syndromes:  familial  LCAT  deficiency  (FLD)  and  fish  eye  disease  (FED).FLD  is  characterized  by  corneal  opacities,  anemia,  and  proteinuria  that  may  progress  to  renal  failure.  Foam  cells  and  membrane-bound  vesicles,  which  appear  to  be  composed  of  cholesterol  and  phospholipid,  accumulate  in  many  tissues  including  the  cornea,  kidneys,  liver,  spleen,  bone  marrow,  and  arteries.  Target  cells  containing  abnormally  high  amounts  of  unesterified  cholesterol  and  lecithin  are  present.  Plasma  contains  high  levels  of  unesterified  cholesterol  and  phospholipids  and  low  concentrations  of  plasma  cholesteryl  esters  and  lysophosphatidylcholine.  Plasma  triglycerides  are  normal  to  increased,  low  density  lipoprotein  (LDL)  levels  are  reduced,  and  high-density  lipoprotein  (HDL)  levels  are  markedly  decreased.  The  morphology  of  the  lipoproteins  is  abnormal,  with  the  presence  in  plasma  of  multilamellar  vesicles,  rouleaux,  LpX-like  particles,  discs,  and  small  spherical  particles.  The  diagnosis  of  FLD  is  confirmed  by  a  virtual  absence  of  plasma  LCAT  activity  in  patients  presenting  with  hypoalphalipoproteinemia,  anemia,  proteinuria,  or  renal  disease.FED  is  characterized  by  corneal  opacities.  The  plasma  triglyceride  levels  are  normal  to  increased,  and  HDL  levels  are  markedly  decreased.  The  diagnosis  of  FED  is  confirmed  by  finding  a  partial  deficiency  of  LCAT  activity  in  the  plasma  of  patients  presenting  with  corneal  opacities  and  marked  hypoalphalipoproteinemia.The  LCAT  gene  is  organized  into  six  exons  interrupted  by  five  introns  and  is  located  on  the  long  arm  of  chromosome  16.  Approximately  40  different  mutations  in  the  LCAT  gene  leading  to  either  FLD  or  FED  have  been  described  to  date.Characterization  of  FLD  and  FED  patients  as  well  as  different  LCAT-transgenic  and  knockout  animal  models  has  demonstrated  an  important  role  for  LCAT  in  modulating  the  metabolism  of  both  HDLs  and  LDLs,  as  well  as  the  development  of  atherosclerosis.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.147
Y2  - 2024/04/24
UR  - ommbid.mhmedical.com/content.aspx?aid=1181449708
ER  -