Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations

Ann Clin Biochem. 2008 Jan;45(Pt 1):102-5. doi: 10.1258/acb.2007.007080.


Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was approximately 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acids / genetics
  • Child
  • Female
  • Humans
  • Hyperlipoproteinemia Type I / blood
  • Hyperlipoproteinemia Type I / enzymology*
  • Hyperlipoproteinemia Type I / genetics*
  • Lipoprotein Lipase / genetics*
  • Lipoprotein Lipase / metabolism
  • Male
  • Middle Aged
  • Mutation / genetics
  • Pedigree


  • Amino Acids
  • Lipoprotein Lipase