FCS

Familial Chylomicronaemia Syndrome (FCS) is a rare genetic disorder.

Advances in knowledge have led to a number of genes being identified which cause a limited ability to metabolise dietary fat. It is called “familial chylomicron – aemia” because it is inherited through families and the condition results in high levels of chylomicrons in the blood. Chylomicrons are triglyceride rich particles so triglyceride levels are also raised.

Triglycerides are another name for fat. Most dietary fat is in the form of triglycerides. Triglycerides and other fatty substances cannot travel “loose” in the blood. So, to move around the body they are packaged into small packages called lipoproteins. These are mixtures of fats (lipids) and proteins. There are a number of different lipoproteins, the largest of which are called chylomicrons. Chylomicrons are rich in triglycerides; they enter the bloodstream from the gastrointestinal tract and their role is to distribute triglycerides, cholesterol, and other lipids to the liver and other locations in the body.

Under normal conditions, an enzyme called lipoprotein lipase (LPL) breaks down the chylomicrons as they travel through the blood. This releases the triglycerides for uptake into the muscle and fat tissues around the body.

Familial chylomicronaemia syndrome (FCS) occurs when these chylomicrons cannot be broken down normally. This occurs when LPL doesn’t work correctly, either because it is defective or absent, or because another component it requires does not work. The result is an elevated level of chylomicrons and triglycerides in the blood, i.e., chylomicronaemia. 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. Like FH, FCS is a lipid condition.

• Familial chylomicronaemia syndrome is an autosomal recessive genetic condition. This means that in order to have the condition, a person needs to have inherited two altered genes – one from each parent.
• Nearly one hundred gene alterations have been identified that cause FCS. About 1 in 500 people are thought to carry one of these FCS causing gene alterations.

Most of these alterations are in the genes that code for LPL itself or for apolipoprotein C-II, a cofactor that the enzyme requires to work properly.

Where the syndrome is caused by a disruption to lipoprotein lipase itself it is often 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 a quarter of patients first show symptoms in infancy.
• Individuals with an FCS causing alternation in apolipoprotein C-II tend to show symptoms later than those with a mutation in lipoprotein lipase itself, often in early adulthood.