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Familial chylomicronemia syndrome (FCS) is an underdiagnosed, genetic form of severe hypertriglyceridemia1,2

FCS overview

  • FCS is caused by loss-of-function pathogenic variants in the lipoprotein lipase (LPL) gene and in other genes encoding proteins required for LPL activity3
  • LPL is an enzyme that breaks down triglycerides in chylomicrons (large particles made in the gut to carry dietary fats) and in very-low-density lipoprotein (VLDL) particles (made in the liver to carry endogenous fats)3,4
  • The lack of LPL functionality in people with FCS leads to the accumulation of chylomicrons and to a lesser degree VLDL particles, resulting in extremely elevated triglyceride levels and a very high risk of pancreatitis5-8
  • FCS manifests in a variety of ways, including recurrent abdominal pain, lipaemic plasma (seen after whole blood centrifugation), eruptive xanthomas and lipaemia retinalis6
  • FCS may be confirmed with genetic testing, based on identifying the presence of variants known to severely impair LPL function1

Not a real patient; actor portrayal.

Woman holding hands on stomach

 

Patients with FCS have triglyceride (TG) levels 10 to 100 times the normal level, which can lead to potentially life-threatening pancreatitis3

People with FCS may endure significant burden from multiple misdiagnoses and repeated hospital visits.7,9 Timely diagnosis supported by genetic testing can help reduce this burden.1

Acute pancreatitis (AP) prevalence is reported to be as high as almost 9/10 (60–88%)10,11

In one study, the rate of hospitalisation for AP was reported to be 58.6%12*

Mortality rate associated with recurrent AP is reported to be up to 6%13

Patients with FCS may face debilitating physical and psychosocial symptoms that lead to social withdrawal and difficulty maintaining employment7

*Study included data from 29 patients with FCS. Data collected over a 10-year span (2006-2016).12

Distinguishing between FCS and multifactorial chylomicronemia syndrome

FCS and multifactorial chylomicronemia syndrome (MCS) are two forms of chylomicronemia syndrome that share clinical features such as very high TG levels, lipaemia retinalis, eruptive xanthomas and AP, but present key differences such as:1,10,14

  • Aetiology: while FCS is caused by biallelic or digenic loss-of-function variants in genes coding for LPL or proteins critical for LPL function, MCS arises from a combination of genetic predisposition and secondary/environmental risk factors for hypertriglyceridemia
  • Pancreatitis: FCS is associated with the highest risk of pancreatitis and associated morbidity and mortality
  • Treatment: Conventional TG-lowering therapies (such as omega-3 fatty acids, fibrates, niacin) typically have little to no effect in FCS, while some TG-lowering effect may be seen in patients with MCS

Accurate diagnosis may lead to more prompt and aggressive management of patients with chylomicronemia syndrome.15

Feature/characteristicFCS (also known as Fredrickson type I hyperlipoproteinaemia and lipoprotein lipase deficiency)1MCS (also known as Fredrickson type V hyperlipoproteinaemia)16
Triglyceride levels>880 mg/dL
(persistent; typically 10–100 times the normal level)3,17		>880 mg/dL
(often intermittent; these patients mostly present with mild HTG between decompensations)6,17
Response to traditional lipid-lowering therapy*No effect10Mild to moderate effect10
Genetic basisBiallelic or digenic loss-of-function variants in genes coding for LPL or proteins critical for LPL function10,17Heterozygous pathogenic variants in FCS-associated genes and/or a high polygenic risk score for elevated TGs† 10,17,18
Age of onsetPaediatric or early adolescence10Adulthood10
Body mass index (BMI)Often normal10Often overweight or obese10
Role of secondary/environmental (non-genetic) factorsMinor contribution; may modulate severity but not disease development10,17Major contribution; a combination of genetic predisposition and secondary/environmental factors modulate both disease development and severity10,17
Population frequency1–19 per 1 million people171700–4000 per 1 million people17

*Traditional lipid-lowering drugs, i.e. statins, fibrates, niacin, omega-3 fatty acids10

†Accumulation of common, small-effect single nucleotide polymorphisms across the genome affecting TG levels18

Diagnosing FCS

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References

  1. Javed F, et al. J Clin Lipid. 2025;19:382-403.

  2. Larouche M, et al. Curr Opin Endocrinol Diabetes Obes. 2025;32(2):75-88.

  3. Gaudet D, et al. N Engl J Med. 2014;371:2200-2206. doi: 10.1056/NEJMoa1400284.

  4. Feingold KR. Endotext [Internet]. 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK305896/

  5. Ginsberg HN, et al. Eur Heart J. 2021;42(47):4791-4806.

  6. Moulin P, et al. Atherosclerosis. 2018;275:265-272.

  7. Davidson M, et al. J Clin Lipidol. 2018;12:898-907.

  8. Valdivielso P, et al. Eur J Intern Med. 2014;25;689–694.

  9. WHAT IS FAMILIAL CHYLOMICRONEMIA SYNDROME (FCS). Available at: www.endocrine.org/-/media/endocrine/files/patient-engagement/infographics/familial_chylomicronemia_syndrome.pdf Accessed: October 2025.

  10. Bashir B, et al. Metabolites. 2023;13(5):621. doi: 10.3390/metabo13050621

  11. Baass A, et al. J Intern Med. 2020;287: 340–348.

  12. Belhassen M, et al. J Clin Endocrinol Metab. 2021;106(3):e1332-e1342.

  13. Gaudet D, et al. J Clin Lipidol. 2016;10(3):680–681.

  14. D'Erasmo L, et al. Arterioscler Thromb Vasc Biol. 2019;39(12):2531-2541.

  15. Pallazola VA, et al. Eur J Prev Cardiol. 2020;27(19):2276-2278.

  16. Paquette M, Bernard S. Front Cardiovasc Med. 2022;9:886266.

  17. Brinton E, et al. Atherosclerosis 2025;403:119114.  doi: 10.1016/j.atherosclerosis.2025.119114.

  18. Hegele R, et al. Curr Opin Lipidol. 2025;36:96–103.

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