TY  - CHAP
M1  - Book, Section
TI  - Familial Lipoprotein Lipase Deficiency, Apo C-II Deficiency, and Hepatic Lipase Deficiency
A1  - Brunzell, John D.
A1  - Deeb, Samir S.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Three  inherited  disorders  have  been  described  in  which  chylomicrons  accumulate  in  plasma:  familial  lipoprotein  lipase  deficiency  (MIM  238600),  familial  apolipoprotein  C-II  deficiency  (MIM  207750),  and  familial  inhibitor  to  lipoprotein  lipase  (MIM  118830).  Chylomicronemia  can  also  occur  in  individuals  with  common  familial  forms  of  hypertriglyceridemia  who  also  have  an  acquired  cause  of  hypertriglyceridemia  such  as  untreated  diabetes  mellitus,  estrogen  or  antihypertensive  drug  therapy,  or  alcohol  use.Familial  lipoprotein  lipase  deficiency  is  a  rare  autosomal  recessive  disorder  characterized  by  absence  of  LPL  activity  and  a  massive  accumulation  of  chylomicrons  in  plasma  and  a  corresponding  increase  of  plasma  triglyceride  concentration.  The  concentration  of  VLDL  may  be  fairly  normal.  The  disease  is  usually  detected  in  childhood  based  on  repeated  episodes  of  abdominal  pain,  recurrent  attacks  of  pancreatitis,  eruptive  cutaneous  xanthomatosis,  and  hepatosplenomegaly.  The  severity  of  symptoms  is  proportional  to  the  degree  of  chylomicronemia,  which,  in  turn,  is  dependent  on  dietary  fat  intake.  Over  60  structural  defects  in  the  lipoprotein  lipase  gene  have  been  demonstrated  to  cause  deficiency  of  the  activity  of  lipoprotein  lipase.  This  lipolytic  enzyme  is  present  on  vascular  endothelial  cells  of  extrahepatic  tissues  and  is  essential  for  hydrolysis  of  chylomicron  and  VLDL  triglycerides  to  provide  free  fatty  acids  to  tissues  for  energy.  The  enzyme  is  released  into  the  blood  by  heparin  and  can  be  assayed  in  postheparin  plasma  or  directly  in  biopsies  of  adipose  tissue.  Diagnosis  is  based  on  low  or  absent  enzyme  activity  in  an  assay  system  that  excludes  other  lipolytic  enzymes  and  contains  normal  plasma  or  apoprotein  C-II,  a  necessary  cofactor  of  the  enzyme;  diagnosis  is  confirmed  by  demonstration  of  a  defect  in  the  structure  of  the  lipoprotein  lipase  gene.  The  disorder  is  probably  not  associated  with  atherosclerotic  vascular  disease,  but  recurrent  pancreatitis  may  threaten  the  patient's  life.  Restriction  of  dietary  fat  to  20  g/day  or  less  is  usually  sufficient  to  reduce  plasma  triglyceride  levels  and  keep  the  patient  free  of  symptoms.  Available  lipid-lowering  drugs  are  not  effective.  Heterozygotes  exhibit  a  50  percent  decrease  of  lipoprotein  lipase  in  postheparin  plasma  but  have  normal  or  only  slightly  abnormal  plasma  lipid  levels.Familial  apolipoprotein  C-II  deficiency  is  a  very  rare  autosomal  recessive  disorder  in  which  apo  C-II  is  absent,  the  clearance  of  chylomicrons  from  the  blood  is  greatly  impaired,  and  triglycerides  accumulate  in  plasma.  VLDL  may  also  be  elevated.  The  disorder  is  diagnosed  in  children  or  adults  based  on  recurrent  attacks  of  pancreatitis  or  by  detection  of  milky  fasting  plasma  on  screening.  Over  10  structural  defects  in  the  apolipoprotein  C-II  gene  have  been  associated  with  absence  of  or  production  of  defective  apolipoprotein  C-II,  a  cofactor  for  lipoprotein  lipase.  Absence  of  this  protein  creates  a  functional  enzyme  deficiency  with  accumulation  of  the  substrate  lipoproteins  in  the  blood.  The  diagnosis  is  based  on  assay  of  lipoprotein  lipase  activity  in  postheparin  plasma  and  on  gel  electrophoresis  of  VLDL  apolipoproteins.  Transfusion  of  normal  plasma  into  the  patient  is  followed  by  a  dramatic  fall  in  the  plasma  triglyceride  level.  Treatment  involves  use  of  a  moderate  fat-restricted  diet  throughout  life.  In  the  case  of  severe  pancreatitis,  transfusion  of  normal  plasma  may  be  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181449576
ER  -