About Severe Hypertriglyceridemia FCS and Genetic Disorders

Learn More About Genetic Testing for Familial Chylomicronemia Syndrome

Download the FCS Genetic Testing Brochure

Genetic disorders
causing sHTG

Familial chylomicronemia syndrome

A small number of people with severe hypertriglyceridemia (sHTG) have a condition called familial chylomicronemia syndrome (FCS).1

People with FCS have genetic variants that severely impair the body’s ability to remove triglycerides from the blood stream.
This condition leads to the build-up of large triglyceride-containing particles called chylomicrons in the blood.1,8.  People with FCS have very high risk for pancreatitis and must severely restrict fats in their diet.8

Other symptoms or signs of FCS can include: 8

  • Abdominal pain due to pancreatitis
  • Loss of feeling in the feet or legs, and memory loss, which can be signs of nerve damage
  • Yellowish, waxy-like deposits of fatty material in the skin, called xanthomas
  • Fatty deposits in the retina of the eye
  • An enlarged liver or spleen
  • In blood samples, a creamy layer will appear after the blood is spun in a laboratory machine
  • Depression, anxiety, and interference with social activities and interpersonal relationships

What is the role of genes in FCS? 12,13

There are at least seven genes associated with FCS. All of them affect the function of the protein lipoprotein lipase (LPL), essential for removing triglycerides from blood.
Variations in the LPL gene cause about 8 in 10 cases of FCS. Research may find other genes linked to FCS in the future.

Genetic testing for FCS

Ionis Pharmaceuticals is sponsoring confidential genetic testing for people with sHTG that meet the following criteria:

  • At least 2 consecutive fasting triglyceride levels above 880 mg/dL at the time of screening
  • No secondary causes or medical conditions known to cause HTG

Possible new ways of treating FCS and other causes of sHTG are under investigation. In the future, genetic testing may help determine who is eligible for such treatments if they are shown to be safe and efficacious.

You can talk to a doctor about whether you are eligible for genetic testing through PreventionGenetics.

Dysbetalipoproteinemia 1,14

Another genetic disorder that causes sHTG is dysbetalipoproteinemia.

People with dysbetalipoproteinemia have variations in a gene known as ApoE. They typically have both very high cholesterol levels and very high triglyceride levels. They are also at high risk for pancreatitis.

A common symptom of dysbetalipoproteinemia is the presence of raised, waxy-appearing, often yellowish-colored blemishes on the skin.

Even though dysbetalipoproteinemia is a genetic disorder, it can usually be diagnosed without genetic testing.

Show References
 
  • 1. Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J. 2020;41(1):99-109c.
  • 2. Ginsberg HN, Packard CJ, Chapman MJ, Borén J, Aguilar-Salinas CA, Averna M, 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;42(47):4791-806.
  • 3. Virani SS, Morris PB, Agarwala A, Ballantyne CM, Birtcher KK, Kris-Etherton PM, et al. 2021 ACC Expert Consensus Decision Pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia: A report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021.
  • 4. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626-35.
  • 5. Packard CJ. Remnants, LDL, and the quantification of lipoprotein-associated risk in atherosclerotic cardiovascular disease. Curr Atheroscler Rep. 2022;24(1534-6242 (Electronic)):133-42.
  • 6. Wang Y. Higher fasting triglyceride predicts higher risks of diabetes mortality in US adults. Lipids Health Dis. 2021;20(1):181.
  • 7. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350.
  • 8. Chyzhyk V, Brown AS. Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis. Trends Cardiovasc Med. 2020;30(2):80-5.
  • 9. National Lipid Association. Lifestyle changes to reduce triglycerides: Advice from the National Lipid Association Clinician’s Lifestyle Modification Toolbox. https://www.lipid.org/sites/default/files/lifestyle_changes_to_reduce_triglycerides.final_edits.7.17.16_0.pdf.
  • 10. Santos-Baez LS, Ginsberg HN. Hypertriglyceridemia-causes, significance, and approaches to therapy. Front Endocrinol (Lausanne). 2020;11:616.
  • 11. Sandesara PB, Virani SS, Fazio S, Shapiro MD. The forgotten lipids: Triglycerides, remnant cholesterol, and atherosclerotic cardiovascular disease risk. Endocr Rev. 2019;40(2):537-57.
  • 12. Carrasquilla GD, Christiansen MR, Kilpeläinen TO. The genetic basis of hypertriglyceridemia. Curr Atheroscler Rep. 2021;23(8):39.
  • 13. Dron JS, Dilliott AA, Lawson A, McIntyre AD, Davis BD, Wang J, et al. Loss-of-function CREB3L3 variants in patients with severe hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 2020;40(8):1935-41.
  • 14. Javvaji A, Can AS, Sharma S. Dysbetalipoproteinemia. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
  • 15. Moulin P, Dufour R, Averna M, Arca M, Cefalù AB, Noto D, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an "FCS score". Atheroscler. 2018;275:265-72.
  • 16. Nawaz H, Koutroumpakis E, Easler J, Slivka A, Whitcomb DC, Singh VP, et al. Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. Am J Gastroenterol. 2015;110(10):1497-503.
  • 17. Stroes E, Moulin P, Parhofer KG, Rebours V, Löhr JM, Averna M. Diagnostic algorithm for familial chylomicronemia syndrome. Atheroscler Suppl. 2017;23:1-7.
  • 18. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33.
  • 19. Koehler EM, Schouten JN, Hansen BE, Hofman A, Stricker BH, Janssen HL. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol. 2013;11(9):1201-4.
  • 20. Nivukoski U, Niemelä M, Bloigu A, Bloigu R, Aalto M, Laatikainen T, et al. Combined effects of lifestyle risk factors on fatty liver index. BMC Gastroenterol. 2020;20(1):109.
  • 21. Paquette M, Bernard S. The evolving story of multifactorial chylomicronemia syndrome. Front Cardiovasc Med. 2022;9:886266.
  • 22. Vincent AM, Hinder LM, Pop-Busui R, Feldman EL. Hyperlipidemia: a new therapeutic target for diabetic neuropathy. J Peripher Nerv Syst. 2009;14(4):257-67.
  • 23. Benefits of physical activity: Center for Disease Control and Prevention. [https://www.cdc.gov/physicalactivity/basics/pa-health/index.htm.
  • 24. Tari AR, Nauman J, Zisko N, Skjellegrind HK, Bosnes I, Bergh S, et al. Temporal changes in cardiorespiratory fitness and risk of dementia incidence and mortality: a population-based prospective cohort study. Lancet Public Health. 2019;4(11):e565-e74.
  • 25. Whole person health: What you need to know: National Center for Complementary and Integrative Health. [https://www.nccih.nih.gov/health/whole-person-health-what-you-need-to-know.
  • 26. Berglund L, Brunzell J, Sacks FM. Patient information page from The Hormone Foundations. Patient guide to the assessment and treatment of hypertriglyceridemia (high triglycerides). J Clin Endocrinol Metab. 2012;97(9):31a-2a.
  • 27. Ito MK. Chapter 6. Patient-centered care. In: Gogia S, editor. Fundamentals of Telemedicine and Telehealth: Academic Press; 2020:115-126.
  • 28. Barry MJ, Edgman-Levitan S. Shared decision making--pinnacle of patient-centered care. N Engl J Med. 2012;366(9):780-1.
  • 29. Elwyn G, Frosch D, Thomson R, Joseph-Williams N, Lloyd A, Kinnersley P, et al. Shared decision making: a model for clinical practice. J Gen Intern Med. 2012;27(10):1361-7.
  • 30. Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 2. J Clin Lipidol. 2015;9(6 Suppl):S1-122.e1.
  • 31. Banerji A, Anderson J, Johnston DT. Optimal management of hereditary angioedema: Shared decision-making. J Asthma Allergy. 2021;14:119-25.
  • 32. Zeman H, Cavanaugh E, Metallinos-Katsaras E, Ireland K, Pojednic R. Improved long-term outcomes in high-risk patients receiving registered dietitian nutritionist care. Endocr Metab Sci. 2021;2:100078.
  • 33. Morrell J, Wierzbicki T. 10 Steps before you refer for: Lipids. Br J Cardiol. 2009;16:242-5.
  • 34. Davidson M, Stevenson M, Hsieh A, Ahmad Z, Roeters van Lennep J, Crowson C, et al. The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study. J Clin Lipidol. 2018;12(4):898-907.e2.
  • 35. Lipid Panel: Cleveland Clinic. [https://my.clevelandclinic.org/health/diagnostics/17176-lipid-panel.
  • 36. Academy of Nutrition and Dietetics. Medical nutrition therapy (MNT) systematic review [https://www.andeal.org/topic.cfm?menu=3949.

Your are about to leave KnowYourTGs.com

You will be taken to a website independently operated and not managed by Ionis Pharmaceuticals. Ionis Pharmaceuticals assumes no responsibility for the content of the site.

Thank you for visiting KnowYourTGs.com