What causes type I hyperlipoproteinemia?

Updated: Jul 23, 2021
  • Author: Mary Ellen T Sweeney, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Type I hyperlipoproteinemia is the best-characterized genetic cause of hypertriglyceridemia and is caused by a deficiency or defect in either the enzyme lipoprotein lipase or its cofactor, apo C-II. Lipoprotein lipase hydrolyzes triglycerides in chylomicrons and very low-density lipoprotein (VLDL), releasing free fatty acids. The enzyme is found in the endothelial cells of capillaries and can be released into the plasma by heparin. Lipoprotein lipase is essential for the metabolism of chylomicrons and VLDL, transforming them into their respective remnants. Apo C-II, an apolipoprotein present in both chylomicrons and VLDL, acts as a cofactor in the action of lipoprotein lipase.

The above pathway is affected by other genetic disorders, particularly type 1 or type 2 diabetes, because lipoprotein lipase requires insulin for full activity. That is, a secondary cause of hyperlipidemia, “second hit,” must be present for the dysbetalipoproteinemia to develop. In addition, the patient may be taking medications, such as protease inhibitors or tricyclic antidepressants, that exacerbate hyperlipidemia.

Two more recently described syndromes include mutations in ApoAV leading to a truncated ApoAV devoid of a lipid-binding domain and glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GP1HBP1) causing decreased binding to LPL and reduced hydrolysis of chylomicrons. [17]

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