Familial Chylomicronemia Syndrome - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder that affects 1 to 2 people per million. It manifests as increased plasma chylomicrons and triglycerides. Affected individuals usually have high triglycerides and chylomicrons in the blood, which can cause various symptoms. Triglyceride levels that are too high can cause various symptoms, including severe episodes of acute pancreatitis. People with familial chylomicronemia syndrome report a lower quality of life as a result of both the symptoms of the disease and the requirement to follow an extremely low-fat diet.

What Is Familial Chylomicronemia Syndrome?

Familial chylomicronemia syndrome (FCS) is a genetic condition in which a person has a lipoprotein lipase gene defect. This gene defect results in extremely high triglyceride levels, which in turn cause stomach pain and fat deposits under the skin. It is a serious disease in which the body is unable to break down dietary fats or triglycerides. These triglycerides are transported throughout the body by large structures known as chylomicrons. Chylomicrons aid in the transport of triglycerides to various parts of the body for energy and fat storage. It can also cause issues with the pancreas and liver, which can eventually cause diabetes.

Familial chylomicronemia syndrome (FCS) has been known by different names. It includes the following.

• Lipoprotein lipase deficiency (LPLD).

• Familial hyperchylomicronemia.

• Chylomicronemia.

• Type 1 hyperlipoproteinemia.

• Endogenous hypertriglyceridemia.

• Chylomicronemia syndrome.

• Type 1 hyperlipoproteinemia.

What Causes Familial Chylomicronemia Syndrome?

Mutations in lipoprotein lipase cause familial hyperchylomicronemia syndrome, a rare autosomal metabolic disorder. Approximately 80 percent of cases of familial hyperchylomicronemia syndrome are caused by inherited defects in the lipoprotein lipase gene. The remaining 20 percent is due to a mutation in other genes involved in lipoprotein-lipase function, including apolipoprotein A-V (APOA5), high-density lipoprotein binding protein 1 (GP1HBP1), apolipoprotein C-II (APOC2), and lipase maturation factor 1 (LMF1).

Triglycerides are broken down by lipoprotein lipase (LPL). Lipoprotein lipase function is impaired in individuals with familial chylomicron syndrome due to mutations in the gene that codes for lipoprotein lipase or mutations in genes that code for other proteins required for lipoprotein lipase to function properly. As a result, triglycerides build up in the blood. Triglycerides are primarily transported by dietary lipids known as chylomicrons. Chylomicrons remain intact and accumulate in the plasma of FCS patients. Chylomicron accumulation can reduce blood flow through the pancreas, resulting in acute pancreatitis. Along with other symptoms and complications, acute pancreatitis may cause pancreatic damage or be fatal.

How Is Familial Chylomicronemia Syndrome Inherited?

FCS is a rare autosomal recessive metabolic disorder. A child develops familial chylomicronemia syndrome when they inherit the defective gene from both parents. As it is a very rare disease, the exact etiology and the mode of inheritance are yet to be explored more.

What Are the Symptoms Associated With Familial Chylomicronemia Syndrome?

The common symptoms observed in patients with familial chylomicronemia syndrome are the following.

• Abdominal pain.

• Indigestion.

• Xanthomas (fatty deposits in the skin).

• Weakness.

• Acute pancreatitis.

• Bloating.

• Diarrhea.

• Impaired memory.

• Concentration issues.

• Anxiety.

• Fatigue.

• Nausea.

• Lipemia retinalis (appearance of "milky" retinal veins in the eyes).

• Numbness in the legs or feet.

How Is Familial Chylomicronemia Syndrome Diagnosed?

There is no specific test to diagnose familial chylomicronemia syndrome (FCS), but it can be diagnosed clinically. High levels of triglycerides and recurrent pancreatitis attacks may indicate FCS as the underlying condition. A complete fasting lipid profile is usually done for diagnosis. Blood triglycerides should be greater than 880 mg/dl for three consecutive blood draws for diagnosis. Though conditions other than familial chylomicronemia syndrome can cause elevated triglyceride levels, hypertriglyceridemia that is resistant to triglyceride-lowering therapy should raise the possibility of familial chylomicronemia syndrome.

Patients with recurrent abdominal pain should undergo computed tomography (CT) to rule out pancreatitis and its complications. A right upper quadrant ultrasound should also be performed to look for gallstones, which could be the cause of pancreatitis.The diagnosis of familial chylomicronemia syndrome is finally confirmed by detecting pathogenic gene variants in lipoprotein lipase (LPL) with either low or no lipoprotein lipase enzyme activity.

How Is Familial Chylomicronemia Syndrome Treated?

Dietary changes are the mainstay of treatment for familial chylomicronemia syndrome. Fibrates, niacin, and omega-3 fatty acids play little to no role in the treatment because they either reduce VLDL (very low-density lipoprotein) or increase lipoprotein lipase activity. Both mechanisms will have no effect on FCS chylomicrons. As a result, patients should eat a low-fat diet. The affected individual's daily fat intake should be kept to less than 15 to 20 grams or 10 to 15 percent of total daily calories. Avoiding alcohol and simple, refined carbohydrates, like those in soda and candy, is also crucial for preventing further increases in triglycerides.

In patients with FCS, conventional triglyceride-lowering drugs frequently fail to reduce triglycerides. Currently, there are no approved drugs for the treatment of familial chylomicronemia syndrome in particular. The affected individuals must avoid medications that are known to raise triglyceride levels. It includes diuretics, estrogens, steroids, high blood pressure medications, antidepressants, medications that suppress the immune system, fish oil supplements, and some heart medications.

The purpose of the dietary modification is to maintain triglyceride levels below the acute pancreatitis cutoff (between 750 mg/dl and 880 mg/dl). Frequently, the diet plan is so strict that the patients need help following it consistently. Thus, counseling and close monitoring with a dietician, an endocrinologist, and a lipidologist are required.

What Are the Complications Associated With Familial Chylomicronemia Syndrome?

Pancreatitis is a painful condition that can lead to long-term organ damage or insulin-dependent diabetes. Pancreatitis caused by extremely high triglyceride levels is the most severe complication of familial chylomicronemia syndrome (FCS) if left untreated. The majority of FCS patients develop pancreatitis. Many of them will experience recurring attacks. Untreated chronic symptoms cause further complications that can result in fatal pancreatitis.

Conclusion

Familial chylomicronemia syndrome is a rare inherited metabolic disease. Affected individuals usually have increased plasma chylomicrons and triglycerides. Mutations in lipoprotein lipase cause familial hyperchylomicronemia syndrome. Dietary modifications are the main treatment for patients with this condition.