Chylomicronaemia--current Diagnosis and Future Therapies

Nat Rev Endocrinol. 2015 Jun;11(6):352-62. doi: 10.1038/nrendo.2015.26. Epub 2015 Mar 3.

Abstract

This Review discusses new developments in understanding the basis of chylomicronaemia--a challenging metabolic disorder for which there is an unmet clinical need. Chylomicronaemia presents in two distinct primary forms. The first form is very rare monogenic early-onset chylomicronaemia, which presents in childhood or adolescence and is often caused by homozygous mutations in the gene encoding lipoprotein lipase (LPL), its cofactors apolipoprotein C-II or apolipoprotein A-V, the LPL chaperone lipase maturation factor 1 or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1. The second form, polygenic late-onset chylomicronaemia, which is caused by an accumulation of several genetic variants, can be exacerbated by secondary factors, such as poor diet, obesity, alcohol intake and uncontrolled type 1 or type 2 diabetes mellitus, and is more common than early-onset chylomicronaemia. Both forms of chylomicronaemia are associated with an increased risk of life-threatening pancreatitis; the polygenic form might also be associated with an increased risk of cardiovascular disease. Treatment of chylomicronaemia focuses on restriction of dietary fat and control of secondary factors, as available pharmacological therapies are only minimally effective. Emerging therapies that might prove more effective than existing agents include LPL gene therapy, inhibition of microsomal triglyceride transfer protein and diacylglycerol O-acyltransferase 1, and interference with the production and secretion of apoC-III and angiopoietin-like protein 3.

Publication types

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

MeSH terms

  • Benzimidazoles / therapeutic use
  • Diet Therapy*
  • Fibric Acids / therapeutic use
  • Genetic Therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type I / diagnosis*
  • Hyperlipoproteinemia Type I / genetics
  • Hyperlipoproteinemia Type I / therapy*
  • Hyperlipoproteinemia Type V / diagnosis
  • Hyperlipoproteinemia Type V / therapy*
  • Hypolipidemic Agents / therapeutic use*
  • Niacin / therapeutic use
  • Plasma Exchange
  • Plasmapheresis

Substances

  • BMS201038
  • Benzimidazoles
  • Fibric Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Niacin