Fast Facts: Familial Chylomicronemia Syndrome

Raising Awareness of a Rare Genetic Disease

Michael H. Davidson, Lane Benes, Anthony S. Wierzbicki, M.H. Davidson, L. Benes, A.S. Wierzbicki

• Publisher: S. Karger
• Year: 2021
• Print ISBN:
  9783318069846
• eBook ISBN:
  9783318069853
• Topic: Medicine
• Subtopic: Gastroenterology & Hepatology

Familial chylomicronemia syndrome (FCS) is an ultra-rare genetic disorder characterized by the abnormal build-up of chylomicrons, the largest type of lipoprotein, which transport dietary fat from the gut to the rest of the body. Patients with FCS often experience severe symptoms, the most feared of which is acute, potentially life-threatening, pancreatitis. This resource is intended to raise awareness of FCS among all members of the healthcare team who come into contact with patients with FCS, with the aim of earlier diagnosis and management, thus preventing some of the more devastating physical, neurological and cognitive symptoms of the disorder.

4	Management and prevention

FCS is characterized by extreme hypertriglyceridemia, which causes physical, neurological and psychosocial symptoms (see Chapter 3), all of which need to be managed and, if possible, prevented. A summary of FCS management is provided in Table 4.1.

TABLE 4.1

Management of FCS

FCS population	Management recommendation
All populations	•Establish a multidisciplinary healthcare team to manage FCS and develop an individualized treatment plan •Eat a very-low-fat diet: < 20 g fat per day or < 10–15% daily caloric intake •Avoid alcohol •Avoid drugs known to increase TG levels •Measure plasma TG levels on a routine basis
Episodes of acute pancreatitis	•Hydrate patients with intravenous fluids •Once attack has subsided, slowly reintroduce very-low-fat diet •Consider insulin therapy in hyperglycemic patients •Some experts recommend a low threshold to initiate plasmapheresis or plasma exchange until serum TG is > 5.65–11.3 mmol/L (500–1000 mg/dL); there are small risks associated with this, including transfusion reaction if plasma products are given back during plasma exchange
Diabetes	•Control blood sugar; insulin is usually necessary due to pancreatic insufficiency •Check levels of vitamins A, E, K and D regularly
Pregnancy	•Maintain fasting plasma TG levels at < 5.65 mmol/L (500 mg/dL) •Limit fat intake to < 2 g/day from weeks 13 to 40 of pregnancy •Use supplements to promote preferential intake of medium-chain fatty acids* •Maintain adequate hydration and electrolyte balance
Pregnancy and diabetes	•Control blood glucose and TG levels •Monitor TG levels weekly •Check for eruptive xanthomas and lipemia retinalis
Pediatrics	•Limit fat to < 15% of total daily caloric intake •Use supplements to promote preferential intake of medium-chain TGs* •Feed infants (0–12 months) a low light-chain/high medium-chain fatty acid formula or skim and fortified expressed breast milk* •Transition 1–2 year olds to skim milk and age-appropriate low-fat solid foods •Monitor growth using age-appropriate charts •Re-evaluate diet at each developmental stage and adjust for age and growth
Psychosocial	•Psychological and nutritional counseling •Connect to support groups, patient organizations and websites for support and to maintain social connections
*Medium-chain TGs are metabolized through a chylomicron-independent pathway.^2

The key goal of managing FCS is to maintain plasma TG levels below 11.3 mmol/L (1000 mg/dL).¹ Patients with FCS do not usually respond to standard lipid-lowering medications. A very-low-fat diet and regular exercise are therefore the mainstays of treatment.

In Europe, an antisense oligonucleotide (ASO) therapy to apo C-III has been licensed for the treatment of FCS (see Medical management below). Other therapies are in development (see Chapter 5).

Multidisciplinary healthcare team

The FCS healthcare team may include a lipidologist, pancreatologist/hepatologist, primary care physician, registered dietitian, psychologist and social worker. Other specialists may also be involved, depending on the patient’s specific medical condition(s). For example, pregnant women with FCS will require the involvement of an obstetrician, pregnant women with both FCS and diabetes will require the involvement of an obstetrician and a diabetologist/endocrinologist, and patients with both FCS and diabetes ought to have the support of a diabetologist/endocrinologist and/or gastroenterologist. In the UK, patients with FCS may be seen at a lipid or inherited metabolic disease clinic that specializes in treating hyperlipidemia and hypertriglyceridemia.

Together, the FCS healthcare team should develop an individual treatment plan for each patient and decide how this information should be communicated to the patient. It is important that healthcare teams meet with the patient and family members to discuss all treatment options and answer questions. This ensures the patient understands the importance of their long-term TG monitoring and follow-up.

Dietary management

To maintain plasma TG levels below 11.3 mmol/L (1000 mg/dL), patients must follow a severely restricted low-fat diet consisting of less than 20 g of fat per day or 10–15% of total caloric intake (Table 4.2). In addition, patients with FCS need to avoid alcohol, which increases TG levels.

When fat is used in the diet, medium-chain TG oils are recommended (although they may be hard to obtain in some countries), as medium-chain TGs are metabolized through a chylomicron-independent pathway,² resulting in lower chylomicron-TG levels.³

TABLE 4.2

Recommended diet for patients with FCS

Dietary recommendations	Foods to eat	Foods to avoid
•Daily fat intake 10–15% of total calories •Eat fat-free or low-fat protein at each meal or snack •Limit total carbohydrates; limit simple carbohydrates •Eat small frequent meals and snacks •Increase water intake •Supplement fat-soluble vitamins (A, D, E, K), as needed	•White fish, some seafood, poultry and lean cuts of meat •Vegetables •Whole grains •Legumes/pulses •Fat-free milk •Fat-free low-sugar dairy products •Fruit •Water	•Alcohol •Simple sugars •Fruit juices

Even with strict adherence to a low-fat diet, which is critical for patients with FCS, 90% of patients with FCS still report symptoms.⁴ Furthermore, 80% of patients report that this diet is very difficult to maintain long term.⁴ It takes an extraordinary amount of meal planning, and social eating is especially challenging.

Deviations from the diet, such as eating dietary fat or consuming alcohol, can result in large fluctuations in serum TG levels that increase the risk of acute pancreatitis, even when patients have followed the restricted diet the majority of the time. These factors contribute to the decreased quality of life reported by patients with FCS.⁵

Physical activity

Regular exercise is important, as it can reduce body fat and TG levels.⁶ In healthy adults, exercise has been shown to induce changes in blood perfusion and increase LPL in exercising muscles. This may therefore lead to increased interactions between chylomicrons and LPL, thus contributing to lower levels of chylomicron-TG⁷ and lower plasma TGs.⁸

Medical management

Standard lipid-lowering medications such as omega-3 fatty acids (or their derivatives), statins and fibrates have a reduced to no effect in patients with FCS.¹ However, as most of these agents have a low side-effect profile it is reasonable to try them. If there is no improvement in TG levels then they should be discontinued. As discussed in Chapter 2, a 3-month trial of a lipid-lowering drug can be used diagnostically, with non-response conf...

Table of contents

• Cover
• Title Page
• Copyright
• Contents
• List of abbreviations
• Introduction
• Terminology, etiology and pathophysiology
• Diagnosis
• Complications
• Management and prevention
• Research directions
• Useful resources
• Index