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About familial chylomicronemia syndrome (FCS)

FCS is a rare genetic disorder of lipid metabolism resulting in severe hypertriglyceridemia and risk of recurrent and potentially fatal pancreatitis (1)

About familial chylomicronemia syndrome (FCS)

FCS is a rare genetic disorder of lipid metabolism resulting in severe hypertriglyceridemia and risk of recurrent and potentially fatal pancreatitis (1)

Patients with FCS have plasma triglyceride (TG) levels ranging from 10 to 100 times the normal value.1* Chylomicrons are formed in the intestines and transport TGs from the intestines to the rest of the body.

FCS is a rare autosomal recessive disease associated with limited functionality of the enzyme lipoprotein lipase (LPL), resulting in accumulation of TG in the blood. The acculmulation of chylomicrons leads to different symptoms and complications. The most severe complication is increased risk of recurrent and potentially fatal acute pancreatitis.1,6

Patients affected by chylomicronemia due to LPL deficiency are at much greater risk of pancreatitis than those with hypertriglyceridemia caused by other conditions, suggesting a direct correlation between accumulation of chylomicrons and pancreatitis.6

FCS affecting daily living

Patients with FCS frequently experience manifestations that have a considerable impact on their daily lives. 75% of patients felt that FCS negatively impacted their social relationships.2

*Optimal TG level up to 1.2 mmol/L (100 mg/dL)8

Fatigue

Forgetfulness

Lipaemia retinalis

Vomiting or diarrhoea

Neurological symptoms

such as memory loss and feeling depressed

Frequent abdominal and back pain

Numbness or tingling of digits

Hepatosplenomegaly

Pancreatitisa

Xanthoma2-4

Diagnosing FCS


Due to its rarity, the recognition and correct diagnosis of FCS is challenging.6 Around 67% of patients have described being misdiagnosed.2

blood vials

Normal
blood sample

Lipemic
blood sample

Clinical characteristics to look out for7

  • TG levels > 885 mg/dl (10 mmol/l)
  • Lipemic blood, caused by the presence of greatly elevated plasma chylomicrons, even in the fasting state
  • Severe hypertriglyceridaemia refractory to standard lipid-lowering therapies
  • No secondary causes of high TGs (e.g. alcohol, uncontrolled diabetes)
  • History of acute pancreatitis/abdominal pain of unknown cause

FCS diagnostic tool

A panel of European experts have provided guidance on the diagnostic strategy surrounding FCS and proposed an algorithm-based diagnosis tool for identification of these patients, which can be readily translated into practice.7

Download FCS score tool

FCS pathogenesis1


FCS is associated with limited functionality of lipoprotein lipase (LPL). The loss of functionality in LPL makes the LPL-pathway inefficient and leads to accumulation of chylomicrons in the blood.

LPL pathway is the primary mechanism by which plasma triglycerides (TGs) are hydrolyzed leading to subsequent efficient removal. Apolipoprotein C-III (ApoC-III) modulates triglyceride levels primarily by inhibiting the LPLdependent pathway but also the LPL-independent pathway.

Triglycerides enter the blood plasma from dietary fat absorption in the intestine, in the form of chylomicrons and from the liver in the form of very low density lipoprotein (VLDL) particles.

The loss of function mutations in LPL makes the LPL-pathway inefficient and leads to accumulation of chylomicrons in the blood.

Mode of action of Waylivra
LIVERINTESTINECHYLOMICRONVLDLVESSELREDUCED TRL REMNANT REMOVALCHYLOMICRONEMIAHIGH TG LEVELApoC-IIIApoC-IIILPL-INDEPENDENT PATHWAYHYDROLYSISLPL-DEPENDENT PATHWAYLPL*

References

  1. Gaudet D, Brisson D, T remblay K, Alexander VJ, Singleton W , Hughes SG, Geary RS, Baker BF , Graham MJ, Crooke RM, Witztum JL. T argeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014 Dec 4;371(23):2200-6. doi: 10.1056/NEJMoa1400284. PMID: 25470695.
  2. Davidson M, Stevenson M, Hsieh A, Ahmad Z, Roeters van Lennep J, Crowson C, Witztum JL. The burden of familial chylomicronemia syndrome: Results from the global INFOCUS study. J Clin Lipidol. 2018 Jul-Aug;12(4):898-907.e2. doi: 10.1016/j.jacl.2018.04.009. Epub 2018 Apr 26. PMID: 29784572.
  3. Davidson M, Stevenson M, Hsieh A, Ahmad Z, Crowson C, Witztum JL. The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study . Expert Rev Cardiovasc Ther. 2017 May;15(5):415-423. doi: 10.1080/14779072.2017.1311786. Epub 2017 Apr 4. PMID: 28338353.
  4. Brunzell JD, Bierman EL. Med Clin North Am 1982;66(2):455–68;
  5. Feingold KR. Introduction to Lipids and Lipoproteins. [Updated 2021 Jan 19]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDT ext.com, Inc.; 2000-. Available from: https://www .ncbi.nlm.nih.gov/books/NBK305896/
  6. Stroes E et al. Atheroscler Suppl 2017;23:1–7.
  7. Moulin P, Dufour R, Averna M, Arca M, Cefalù AB, Noto D, D’Erasmo L, Di Costanzo A, Marçais C, Alvarez-Sala W alther LA, Banach M, Borén J, Cramb R, Gouni-Berthold I, Hughes E, Johnson C, Pintó X, Reiner Ž, van Lennep JR, Soran H, Stefanutti C, Stroes E, Bruckert E. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018 Aug;275:265-272. doi: 10.1016/j.atherosclerosis.2018.06.814. Epub 2018 Jun 18. PMID: 29980054. 
  8. Ginsberg et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021 Dec 14;42(47):4791-4806.