Gastrointestinal distress, recurrent pancreatitis, and skin changes are a few of the symptoms associated with familial chylomicronemia syndrome (FCS), a rare genetic disorder that affects fat metabolism.
FCS occurs when both parents pass on genetic mutations in one or more of the genes responsible for triglyceride metabolism. Triglycerides are a type of fat molecule.
While FCS can affect anyone of any race or gender, it only occurs in about 1 in every 1 to 2 million people.
This article provides an overview of FCS, its causes, and current treatment options.
FCS is an inherited genetic condition. It occurs when mutations in the genes responsible for triglyceride metabolism prevent the body from producing enough of the enzyme lipoprotein lipase (LPL).
FCS features two sets of genetic mutations (biallelic) on a person’s non-sex chromosomes (autosomes) that pass from both parents (recessive). This means it’s an autosomal recessive condition that follows a biallelic inheritance pattern.
FCS occurs when genetic mutations prevent the body from producing enough LPL. Around
Other genes, however, can affect LPL production, including the LMF1, APOA5, and GPAS3 genes. Mutations of these genes and others involved in triglyceride metabolism can also result in FCS.
LPL is an enzyme essential to fat metabolism. After a meal, the small intestine processes dietary fats and packages them into chylomicrons. Chylomicrons are vehicles that carry triglycerides throughout the body through the bloodstream.
LPL breaks chylomicrons down into free fatty acids to be used as energy or stored in fat tissue. Without enough LPL, the volume of triglyceride-dense chylomicrons in the bloodstream becomes too high, resulting in hypertriglyceridemia.
FCS causes clinical signs and various symptoms that affect physical and mental health.
Clinically, doctors detect FCS through blood work when fasting triglyceride levels are above 750 mg/dl (41.6 mmol/L) and haven’t responded to traditional therapies. Blood plasma samples often appear milky-white due to the high triglyceride content.
Persistently high triglyceride levels can cause a variety of symptoms. Triglycerides can accumulate in tissues like the skin, and excess chylomicrons can disrupt blood flow to organs and promote inflammation.
Acute, recurrent pancreatitis is one of the classic symptoms of FCS because of the role the pancreas plays in fat metabolism. LPL typically resides in the vessels of the pancreas, allowing the breakdown of chylomicrons. When chylomicrons don’t break down, they restrict blood flow, cause inflammation, and damage pancreatic tissue over time.
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Pancreatitis can be potentially life threatening if left untreated.
Other symptoms frequently reported in FCS that are not always attributed to pancreatitis include:
- abdominal pain
- nausea
- diarrhea or constipation
- bloating
- physical weakness
- fatigue
- trouble concentrating
- memory problems
- eruptive xanthomas (rash-like bumps on the skin)
- hepatosplenomegaly (enlargement of the liver and spleen)
Doctors diagnose FCS through clinical and genetic testing. Laboratory tests can verify the presence of high triglyceride levels. Healthcare professionals pair laboratory results with a person’s current symptoms and family medical history when considering underlying causes.
When high triglyceride levels do not respond to traditional medications, an inherited disorder is suspected, and genetic testing may be ordered.
FCS-specific gene panel sequencing screens for the known genetic mutations associated with FCS. Although rare, negative genetic results are possible in FCS.
Researchers have not discovered all genetic variations or mutations that cause FCS, and
A trait of FCS is that triglyceride levels do not respond to typical triglyceride-lowering medications. In the past, this meant healthcare teams managed FCS mainly by restricting dietary fats.
In 2024, however, the
Diet modification in FCS means monitoring fat consumption at between 10% and 15% of a person’s daily calories. Total fat consumption should not be more than 15 to 20 grams each day.
Dietary changes may include adding specific types of fats, such as medium-chain triglycerides, which are not incorporated into chylomicrons.
Medium-chain triglycerides are in many foods, including:
- palm kernel oil
- coconut oil
- milk
- yogurt
- nuts and seeds
- cheese
- dark chocolate
- butter
Incorporating essential fatty acids, such as linolenic acid, and fat-soluble vitamins, such as vitamins A and D, into a person’s diet can also help.
Doctors may also make medication changes for people managing coexisting conditions. Beta-blockers, thiazide diuretics, and other drugs used in chronic conditions can cause triglyceride levels to increase.
There is no cure for FCS, but medication, diet modification, and lifestyle changes can help improve a person’s overall quality of life.
Due to the lifelong challenges of this condition and its restrictive dietary management, some people experience challenges related to anxiety or depression.
If left untreated, FCS can cause life threatening pancreatitis and
FCS is a genetic disorder caused when both parents pass on genetic mutations that affect the body’s production of LPL.
Pancreatitis, abdominal pain, skin changes, and fatigue are common symptoms of FCS.
There is no current cure for FCS. However, timely treatment with medications, dietary management, and lifestyle improvements can help reduce its effect on daily life.
