FCS Understanding the Burden

Familial chylomicronemia syndrome, commonly known as FCS, is a rare genetic disorder that results in severe hypertriglyceridemia. FCS is inherited in an autosomal recessive fashion, so two copies of an abnormal gene – one from each parent - must be present for FCS to develop. The most common gene related to FCS is lipoprotein lipase (LPL), an enzyme that works to break down triglycerides. In FCS, the level of LPL is genetically reduced or available LPL does not function properly. This causes a build-up of chylomicrons, lipoprotein particles that facilitate the transport of dietary fat and cholesterol. This build-up of chylomicrons leads to a severe increase in triglyceride levels, increasing the risk of acute pancreatitis, a sometimes life-threatening inflammation of the pancreas that results in severe and debilitating pain. 

Signs and symptoms of FCS can be variable. Some patients may have no warning until they develop acute pancreatitis. Others may have recurrent abdominal pain without pancreatitis. Patients also sometimes develop eruptive xanthomas, which are triglyceride deposits under the skin or in internal organs. Elevated triglyceride levels can cause blood to appear milky and opaque. In women with FCS, factors that increase estrogen levels, including use of oral contraceptives and pregnancy, can cause a further spike in triglycerides, increasing their risk of pancreatitis, miscarriage and maternal fatality.

A recent survey of FCS patients showed that:
  • 59% reported a history of recurrent abdominal pain without hospitalization; and
  • 50% had a history of recurrent pancreatitis (ranging from 2 to 96 episodes).
In a separate study of patients experiencing triglyceride-induced pancreatitis:
  • 60% required care at an intensive care unit;
  • 50% had pancreatic necrosis as identified via contrast CT-scan findings;
  • 48% developed persistent organ failure;
  • (median) hospital stay was 17 days; and
  • there was an 8% mortality rate.

Many people living with FCS report experiencing episodes of fatigue, lack of energy (asthenia), impaired cognition and numbness/tingling. Patients also report that fatigue and pain caused by FCS can affect their ability to work, while dietary restrictions and fear of attacks of pancreatitis can restrict opportunities to participate in many social activities or travel. The fear of pancreatitis causes many patients to limit social interactions, which can lead to feelings of loneliness, isolation and depression. In many cases, even after a diagnosis of FCS patients also do not meet with their physicians regularly because they conclude that there is nothing that can be done to help.

The Path to Diagnosis

While awareness of FCS has expanded in recent years, the path to diagnosis can vary significantly. Some FCS patients are identified in infancy before developing any complications, often after their blood is incidentally noted to be lipemic. Most patients, however, are diagnosed only after developing acute pancreatitis – often multiple times – and eventually being referred to a lipid specialist familiar with FCS.

A diagnosis of FCS should be considered for individuals with sustained severe hypertriglyceridemia. Once hypertriglyceridemia is identified, healthcare providers must rule out all other potential causes (e.g. uncontrolled diabetes, hypothyroidism, alcohol use, estrogen use, corticosteroids) before establishing a diagnosis of FCS.

Genetic confirmation is considered the gold standard for FCS diagnosis, but has several limitations. Availability of genetic testing for FCS is limited to select research laboratories. In the United States, commercial laboratories may not offer genetic screening specifically for FCS. In addition, some FCS patients may harbor mutations that cannot be sequenced with current technology, so the absence of detectable mutations does not rule out FCS.

Despite advances in our ability to identify FCS, many patients remain undiagnosed until later in life or after they have had one or several attacks of pancreatitis. By that time, most patients have lived with the symptoms of FCS for years. Even after an attack of pancreatitis, misdiagnosis is common. Doctors often conclude that a patient’s pancreatitis is caused by other more common factors such as gallstones or excessive alcohol consumption.

Broader education about the symptoms and risks of FCS could help healthcare providers diagnose FCS earlier in many patients, which will play an important role in delivering more appropriate care and effective patient management. For example, in the few cases where FCS is diagnosed in infancy, it has been possible to take steps to try to control triglyceride levels early through use of a restrictive diet and other forms of intervention (e.g. formula high in medium-chain triglycerides). Currently available lipid-lowering therapies – although often used in adults with FCS - are insufficient to help FCS patients reduce triglycerides, primarily because none of the existing drugs affect LPL levels or function.

Current Standard of Care

No approved therapies exist for the treatment of FCS. Current standard of care involves efforts to reduce triglyceride levels by severely restricting dietary intake of fat. Most guidelines suggest that adults with FCS limit dietary intake of total fat to levels as low as 15 grams/day. To put that into perspective, a single teaspoon of peanut butter contains roughly eight grams of fat. As a result, most patients may find the necessary effort to restrict fat intake to be extremely challenging over the long term.

Most clinicians agree that broader use of lipid panel testing to identify patients with high triglycerides can play an increasingly important role in FCS care in the years ahead. This should be supplemented with expanded efforts to help more endocrinologists, emergency room providers, primary care physicians and other healthcare providers be familiar with the symptoms of FCS, the risk of misdiagnosis and the optimal strategies in patient management.

Looking toward the future, there have been some promising recent advances in research targeting new treatment options for FCS. These efforts could lead to new options to reduce triglyceride levels and improve outcomes in symptom management. In addition, another important change in the FCS landscape that is having a positive impact has been the emergence of a robust and active advocacy community that is helping many patients connect with others who understand their challenges and can share support and best practices.

The FCS Foundation offers a range of information and opportunities for patients to connect with other patients from across the United States. In many cases, these platforms represent the very first time that patients have had an opportunity to meet and share information with others affected by FCS.

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