FCS is caused by mutations in the gene encoding lipoprotein lipase (LPL)1. Abnormal LPL function results in decreased breakdown of triglycerides.
Normal triglyceride metabolism1,2
Triglycerides enter the blood plasma from the liver in the form of very lowdensity lipoprotein (VLDL) particles and from dietary fat absorption in the intestine, in the form of chylomicrons.
Lipoprotein lipase (LPL) breaks down triglycerides within chylomicrons, releasing free fatty acids (FFA).
Apolipoprotein C-III (apoC-III) modulates this process primarily by inhibiting the LPL-dependent pathway and one or more LPL-independent pathways of metabolism
The LPL-dependent pathway, leads to the efficient removal of remnants of chylomicrons and VLDL and helps to maintain normal triglyceride levels.
FCS is caused by a mutation in LPL function2
The loss of function mutations in LPL makes the LPL-pathway inefficient and leads to accumulation of chylomicrons in the blood.
VLDL: very low-density lipoprotein, ApoC-III: Apolipoprotein C-III, LPL: lipoprotein lipase, FFA: free fatty acid.
- Brunzell JD, Bierman EL. Med Clin North Am 1982;66(2):455–68;
- Brahm AJ, Hegele RA. Nat Rev Endocrinol 2015;11:352–62
- Davidson M et al. J Clin Lipidol 2018;12(4):898–907