Disease overview

Familial chylomicronemia syndrome is a genetic disorder in which the body does not break down fats correctly.  The disorder is quite rare, occurring in less than 1 to 2 million people, though it is slightly more common in certain areas, as in certain parts of Quebec.  The disease leads to symptoms such as recurrent pancreatitis and fatty deposits in the skin (xanthomas).  (See “Symptoms.”)

The syndrome results in a marked elevation of chylomicrons and triglycerides.  Triglycerides are a kind of lipid, substances that cannot be dissolved in water.   They are taken into the body from the diet in the form of fats and oils. To be transported in the bloodstream, they are packaged with other proteins, called apolipoproteins, as well as with cholesterol molecules and other lipids.  These molecules come together to make up larger structures, termed chylomicrons.  The chylomicrons enter the bloodstream to distribute triglycerides, cholesterol, and other lipids from the gastrointestinal tract to other locations in the body.

Under normal conditions, an enzyme called lipoprotein lipase (LPL) breaks down the chylomicrons as they travel through the capillaries in fat and muscle tissue.   This releases the triglycerides into their component parts for uptake into these tissues.  Familial chylomicronemia syndrome occurs when these chylomicrons cannot be broken down normally.  This occurs when LPL doesn’t work correctly, either because it is itself defective or absent, or because another component it requires doesn’t work.  This results in an elevated level of chylomicrons and triglycerides in the blood, i.e., chylomicronemia.  This is what leads to most of the symptoms of the condition.  The degree of elevation of chylomicrons and triglycerides corresponds with the severity of the symptoms.

Familial chylomicronemia syndrome is an autosomal recessive genetic condition.  In order to have it, a person needs two copies of defective genes—one from each parent. These genes are portions of DNA, the heritable material passed down from parents to children.  About 1 in 500 people are thought to carry one of these defective genes.  Nearly one hundred mutations have been identified that cause the syndrome.

Most of these are mutations in the genes that code for LPL itself or for apolipoprotein C-II, a cofactor that the enzyme requires to work properly.  More commonly the syndrome is caused by a disruption to lipoprotein lipase itself and is termed familial lipoprotein lipase deficiency, or LPLD.   When due to a disruption of apolipoprotein C-II, the condition is called familial apolipoprotein-CII deficiency.  In even rarer cases, the syndrome can result from the presence of an inhibitor to lipoprotein lipase.

LPLD is usually first noted in childhood or early adolescence, but 25% of patients first show symptoms in infancy. Individuals with a mutation in apolipoprotein C-II tend to show symptoms later than those with a mutation in lipoprotein lipase itself, often in early adulthood.

A serious medical condition, familial chylomicronemia syndrome requires lifelong treatment, supervision, and dietary intervention.  However, with proper diagnosis, treatment, and dietary adherence, these patients can lead relatively normal lives.   Though the risk of pancreatitis and other symptoms is not completely eliminated, it can be greatly reduced.  Scientists have targeted gene therapy as a potential treatment of the condition, which may further reduce patients’ symptoms and complications from the disorder.

(See “Treatment.”)

Familial chylomicronemia belongs to a broader class of diseases called dyslipidemias.  In dyslipidemias, cholesterol and/or triglycerides are elevated.  In the case of familial chylomicronemia, this is due to a primary cause—a genetic defect which causes marked elevation of triglycerides.  It is sometimes classified as hyperlipoproteinemia type I, denoting elevation in chylomicrons and triglycerides, without significant elevations in cholesterol or in low-density lipoproteins (LDL)  or very-low-density lipoproteins (VLDL)—two other carrier structures composed of lipids and proteins.