What is FCS and/or LPLD?
Familial chylomicronemia syndrome (FCS) — also referred to as familial LPL deficiency (LPLD), or hyperlipoproteinemia Type 1 — is a very rare hereditary condition. Individuals with FCS lack a properly functioning enzyme called lipoprotein lipase (LPL), that is involved with lipid metabolism. The disruption of the enzyme activity leads to a build-up of triglycerides and chylomicrons (chylomicronemia).1,2
Under normal conditions, triglycerides are packaged into chylomicrons in the intestine and transported to fat and muscle cells. In individuals with FCS, lack of functioning LPL results in their triglycerides not being degraded, which leads to very high concentrations of triglycerides and chylomicrons.1,2
The high concentration of chylomicrons can trigger a host of problems, including the development of skin lesions known as eruptive xanthoma, a creamy appearance of the retinal blood vessels (lipaemia retinalis), abdominal pain, acute recurrent inflammation of the pancreas (pancreatitis), and/or abnormal enlargement of the liver and/or spleen (hepatosplenomegaly).1,2
This very rare disease may go undetected, or may be improperly diagnosed as hypertriglyceridemia during childhood. In many cases, patients are not properly diagnosed until they are young adults and experience severe abdominal pain due to pancreatitis.5
FCS is not yet well understood. More natural history studies and clinical trials are needed to better understand this very rare condition. Natural history studies provide information on how the disease progresses over time and its impact on patients’ daily lives. Clinical trials provide data on the safety and efficacy of treatment options.
An estimated 1 in 1 million people have FCS. However, the exact prevalence is currently unknown since the condition may not get properly diagnosed.1,5 A so-called founder population has been identified in Quebec, Canada and in the Netherlands, and the prevalence of FCS in these populations is as high as 19-20 in 1 million people.
FCS is caused by an autosomal, recessive genetic defect. Both parents must have the mutation, and both parents must pass that mutation on to the child (homozygous). If both parents have the mutation, there is a 25% chance that their child will have FCS.4,5
Individuals with only one mutation (heterozygous) may or may not have hypertriglyceridemia. These individuals may be at increased risk for mixed dyslipidemia with low HDL cholesterol levels and may be susceptible to developing atherosclerosis.7
Due to the rarity of the condition, the natural history of FCS is poorly understood. It is currently believed that most persons with FCS begin to show symptoms early in life (colicky, severe abdominal pain), but may not be diagnosed until their teens or 20’s, when pancreatitis attacks become more frequent. Pancreatitis is a very serious condition and may result in a fatal outcome.
More natural history studies need to be conducted to better understand and recognize earlier, less serious symptoms. Physicians are encouraged to inform their patients with FCS of an FCS registry which they can be part of to help improve the collective understanding of this condition (https://connect.patientcrossroads.org/?org=fnla). This registry is public and data is available to all physicians.