Familial Chylomicronemia Syndrome

Familial chylomicronemia syndrome (FCS) is a rare genetic condition that impacts the ability of the body to break down fats, leading to a buildup of fat known as triglycerides in the blood. FCS is estimated to affect 1 to 10 individuals per 1 million. The diagnosis of FCS can be made based on clinical symptoms and labs, but genetic testing is the only way to actually confirm the diagnosis. ¹ This condition has also been called lipoprotein lipase deficiency or type 1 hyperlipoproteinemia.

Fats are a source of fuel and energy storage for the human body and we consume fat in foods we eat. After we eat fat-containing foods, our body transports fats in the form of triglycerides. Triglycerides are carried in a structure called chylomicrons to areas of the body for energy and storage. Lipoprotein lipase (LPL) is an enzyme that helps to break down the triglycerides so that the fat can be taken up by cells. In patients that have FCS, LPL does not work correctly, so fats cannot be broken down and triglycerides build up in the blood. Usually, triglycerides are ˂150 mg/dL and with FCS it is common to be >750 mg/dL.

Individuals inherit FCS genetically, and usually, it is passed down by both parents. Most individuals with FCS have a mutation which affects the LPL gene.

Clinically, this condition usually shows symptoms in early life but because it is rare and unfamiliar to most healthcare providers, diagnosis can be delayed. The possible signs of FCS in children and adults can include:

• Nausea
• Vomiting
• Abdominal pain
• Pancreatitis
• Lipemia retinalis (abnormal white appearance of the blood vessels at the back of the eye)
• Eruptive xanthomas (small yellow bumps on the skin that can be tender or itchy) and enlarged liver or spleen. 

Factors that might point to a diagnosis of FCS:

• Triglyceride levels in the blood > 750 mg/dL, often in the thousands.

• No alternative explanation of high triglycerides (poorly controlled diabetes, obesity, thyroid disease, liver disease, kidney disease, or some medications).

• Episodes of pancreatitis (inflammation of the pancreas causing severe abdominal pain) which can start in childhood.

• Triglycerides stay elevated even when taking medications to lower them (fish oil, fibrates).

Currently, there are no FDA-approved treatments for FCS. Cholesterol and triglyceride lowering medications such as statins, fibrates, or prescription fish oil are not effective in patients with FCS. A list of clinical trials is listed below.

It is important to closely monitor triglyceride levels, particularly with any changes in diet, medications, nutrition supplements, or in pregnancy. This helps to better inform nutrition recommendations and monitor for risk for acute pancreatitis.

Prescription grade medium-chain triglyceride oil, such as capric and caprylic acid, can be used by people with FCS to give additional fat and calories, while not increasing triglyceride level because capric and caprylic acid are fats that do not use the LPL system that is affected in FCS. Prescription grade MCT oil can be used by people with FCS to give additional fat and calories, while not increasing triglyceride levels.

A registered dietitian nutritionist (RDN) can help individuals ensure they are meeting their nutrition needs while also helping maintain lower triglyceride levels and prevent nutrient deficiencies.

It is important to note that the diet is difficult to follow, and individuals can still experience high triglyceride levels, abdominal pain, and pancreatitis despite following the diet. ³

To manage triglyceride levels, patients with FCS must follow a specialized diet, which includes:

• Very low fat intake: Dietary fat should be <10-15% of daily calories, which is usually <10-20 grams of fat per day for many people. This includes all dietary fats, both saturated and unsaturated fatty acids. It is important to consume enough of the essential fatty acids, linoleic acid and alpha-linolenic acid, to prevent deficiency. Omega-3 fatty acids are sometimes prescribed and used to try to lower triglyceride levels, however studies are not conclusive on their use. If omega-3 fatty acids are used, the dose must be included in overall daily fat limit.
• Limiting or avoiding simple carbohydrates: “Simple” carbohydrates are those high in added sugar and/or low in fiber and include desserts and sugary beverages. Whole grains such as whole wheat bread, brown rice, or quinoa are recommended instead of refined grains.
• Supplementing fat-soluble vitamins, as needed: Vitamins A, D, E, and K are fat-soluble vitamins and need fat to be fully absorbed in the body. With the very low fat diet and changes to fat metabolism, people with FCS may need to supplement these vitamins to prevent deficiency.
• Avoiding alcohol: Alcohol can increase the risk of pancreatitis.

Working with a lipid specialist with experience or expertise in FCS can be very helpful for high quality care and monitoring. You can search for a local lipid specialist through our website: https://www.learnyourlipids.com/find-a-clinician/.

While there are no FDA-approved medications for FCS, there are several ongoing clinical trials testing treatments which can be searched online at https://clinicaltrials.gov. Below are clinical trials evaluating treatments with a link to the trial:

1. Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia
   “The purpose of this trial is to study the long-term efficacy and safety of orlistat for reducing blood triglyceride levels in patients with type 1 hyperlipoproteinemia.”  https://clinicaltrials.gov/study/NCT05816343
2. Olezarsen Early Access Program for Patients With Familial Chylomicronemia Syndrome (FCS)
   “The purpose of the Expanded Access Program is to provide pre-approval access of olezarsen to eligible patients with Familial Chylomicronemia Syndrome (FCS).”  https://clinicaltrials.gov/study/NCT06360237
3. A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
   “The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) from baseline.”  https://clinicaltrials.gov/study/NCT05130450
4. A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
   “The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of olezarsen (formerly known as AKCEA -APOCIII-LRX) in participants with FCS previously treated with volanesorsen.”  https://clinicaltrials.gov/study/NCT05185843
5. Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS) (PALISADE)
   “The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 plozasiran) in adult participants with familial chylomicronemia syndrome (FCS).”  https://www.clinicaltrials.gov/study/NCT05089084

References:

1. Brahm AJ, Hegele RA. Chylomicronaemia – current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11:352–362.
2. Williams, Rhodes, Karmally et al. Familial Chylomicronemia Syndrome: Bringing to life dietary recommendations through the lifespan. J Clin Lipidol. 2018;12(4):908-919. Doi: 10.1016/j.jacl.2018.04.010
3. Gelrud, Williams, Hsieh et al. The burden of familial chylomicronemia syndrome from the patients’ perspective. Expert Rev Cardiovasc Ther. 2017;15(11):879-887. Doi: 10.1080/14779072.2017.1372193.