Currently, there are no FDA approved familial chylomicronemia syndrome treatments. It is a hereditary, serious disease that prevents the body from breaking down fats consumed through the diet, or triglycerides. Familial chylomicronemia syndrome (FCS) is a rare disorder of lipid metabolism characterized by high levels of triglycerides (TGs) due to failure of chylomicron clearance. Traditional treatments to reduce lipid levels such as statins, fibrates, and niacin are not effective in people with FCS because the effectiveness of these medications depends on a functional lipoprotein lipase enzyme. It can be diagnosed by looking for excess alcohol intake, hypertriglyceridemia, uncontrolled diabetes, acute pancreatitis, and abdominal pain.
The most typical sign of FCS is the appearance of fatty blood on the skin, mainly due to high levels of body fat. Individuals with extremely high triglyceride levels are more subjected to familial chylomicronemia syndrome. FCS is an uncommon inherited metabolic disorder found to affect a certain number of individuals per million. It is an advanced disease which prevents the human body from breaking down fat ingested through the diet. These fatty triglycerides are carried by small structures known as chylomicrons, which are responsible for transporting fat between liver cells. Chylomicron cholesterol is accumulated in liver cells where it becomes oxidized and accumulates in certain cells.
The accumulation can cause a variety of life-threatening ailments like heart disease and stroke. Chylomicron cholesterol is formed through the process of Deamination. Deamination is the conversion of cholesterol to bile salts, and is used in fat digestion. Several disorders such as congenital heart diseases and diabetes, as well as nonalcoholic fatty liver disease, are associated with excessive accumulation of cholesterol. In patients with FCS, excessive accumulation of cholesterols in the liver is seen, and this condition was attributed to the hereditary factor of the patients. FCS is a rare autosomal recessive disorder of lipid metabolism characterized by high levels of triglycerides (TGs) due to failure of chylomicron clearance.
FCS is a genetic disorder estimated to affect 1 to 2 individuals per million. FCS is caused by having high triglycerides in the blood, for those who have inherited this genetic disorder from one or both parents. It is a rare disease, and around 95% of rare diseases have no FDA approved treatment. Similarly, there is no FDA-approved familial chylomicronemia syndrome treatment. Familial chylomicronemia syndrome is diagnosed based on fasting triglyceride levels above or 750 mg/dL (8.5 mmol/L), which do not respond to standard lipid-lowering therapy (Brahm and Hegele 2015) and a family history of high plasma triglyceride levels (Brunzell 1993). FCS affects the quality of life of patients and their caregivers.
Severe complications associated with FCS include enlarged spleen, enlarged liver, fatty liver diseases, and pancreatitis, which can be life-threatening. The signs and symptoms of familial chylomicronemia syndrome place a clinical and psychosocial burden on patients and their families and/or caregivers. The U.S. Food and Drug Administration (FDA) refused to approve volanesorsen for the treatment of FCS based on safety issues of thrombocytopaenia and risks of bleeding. Thus, there is an increasing demand for safe, effective familial chylomicronemia syndrome treatment worldwide. Moreover, FCS treatment involves management of both acute exacerbations of chylomicronaemia as well as chronic management to reduce the probability of destabilization.