title: Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat.
abstract: BACKGROUND
  The treatment of familial hyperchylomicronemia presenting in early childhood with episodes of pancreatitis has been ineffective, and affected patients remain at risk for pancreatitis.
  
  
  OBJECTIVE
  To report on the effect of orlistat in siblings with severe inherited hyperchylomicronemia and to assess posttreatment lipoprotein concentrations and composition.
  
  
  METHODS
  Serial observations of plasma lipid levels and hospitalizations after treatment with orlistat and lipoprotein studies on a single fasting posttreatment sample.
  
  
  RESULTS
  The affected siblings inherited a lipoprotein lipase gene mutation from each of their parents: a novel mutation from their father (c.542G > C, p.G181R) and a known missense mutation from their mother (c.644G > A, p.G215E). When the boy presented to us at age 9 years of age and his sister at age 7 years, we found that addition of orlistat, a pancreatic lipase inhibitor, at a dose of 120 mg given before three low-fat meals a day was effective in reducing episodes of pancreatitis in the boy and in maintaining the triglyceride at lower levels in both children. During treatment, the children were observed to have elevations in apolipoprotein (apo)B, low-density lipoprotein particle concentration, abnormal apoB-containing subclasses, and deficiencies in apoA-I and apoA-II-containing lipoproteins, changes consistent with continuing increased cardiovascular risk.
  
  
  CONCLUSIONS
  The data support the need for more effective long-term treatments that not only prevent pancreatitis but also offset cardiovascular risk. Orlistat can be considered effective in augmenting the effect of a low-fat diet and reducing risk for pancreatitis.
authors: Diabetes and Endocrinology Section, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. piersblackett@att.net
authors: Piers
authors: P
authors: Blackett
authors: Jeanie
authors: J
authors: Tryggestad
authors: Sowmya
authors: S
authors: Krishnan
authors: Shibo
authors: S
authors: Li
authors: Weihong
authors: W
authors: Xu
authors: Petar
authors: P
authors: Alaupovic
authors: Carmen
authors: C
authors: Quiroga
authors: Kenneth
authors: K
authors: Copeland
mesh_terms: D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics; D016633:Apolipoprotein A-II / Q000172:deficiency / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood; D002648:Child; D018752:Diet, Fat-Restricted; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000175:diagnosis* / Q000628:therapy; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D000077403:Orlistat; D010195:Pancreatitis / Q000517:prevention & control; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001055:Apolipoproteins B; D004791:Enzyme Inhibitors; D007783:Lactones; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000077403:Orlistat; D008049:Lipase; C518354:PNLIP protein, human; D008071:Lipoprotein Lipase