Rare metabolic process characterized by elevated chylomicrons in the fasting state resulting in a milky appearance to plasma, eruptive xanthomas, and hepatosplenomegaly.
Arare genetic disorder that severely affects the body’s ability to process fats.
A genetic recessive disorder.
Worldwide prevalence of one per hundred thousand persons to one per 1 million persons.
The condition comes in two main forms: familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome.
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive condition that is present from childhood and is characterized by severe hypertriglyceridemia (HTG), with triglyceride (TG) levels >10 mmol/L (>885 mg/dL).
Familial chylomicronemia syndrome is characterized by reduced or absent lipoprotein lipase activity.
Lipoprotein lipase mediates lipolysis of plasma triglycerides in chylomicrons and other triglyceride rich lipoproteins, and its absence leads to fasting and post prandial chylomicronemis with triglyceride levels 10-100 times normal.
Normal triglyceride level is 150 mg/dL.
Familial chylomicronemia syndrome is a result of the inactivating mutations in both alleles of the LPL gene or from mutations and other genes encoding proteins required for LPL activity such apolipoproteina C-III and A-5, glycosylphosphatidylinositol-anchored high density lipoprotein binding1 and lipase maturation factor 1.
Associated with acute and recurrent pancreatitis.
The syndrome is marked by several distinctive features:
Severe hypertriglyceridemia extremely high levels of triglycerides in the blood.
Chylomicron accumulation is caused by changes in genes that impair the normal breakdown of triglycerides carried by chylomicrons.
The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis
Familial chylomicronemia syndrome (FCS) is a rare genetic disorder estimated to affect 1-2 individuals per million.
The condition is caused by mutations in genes that affect lipoprotein lipase function, including LPL, APOC2, APOA5, and other regulatory genes.
Underlying defect is abnormal lipid metabolism with deficiencies of lipoprotein lipase or apoprotein C-III.
Apoprotein C-III is a small glycoprotein, predominantly synthesized by the liver that is a major determinant of triglyceride levels.
Apoprotein C III circulates on the surface of triglyceride rich protein, such as chylomicrons and VLDL‘s and increases triglyceride levels.
Apoprotein C III inhibits life of protein, lipase activity, which prevents the lipolysis of chylomicrons.
Exacerbated by pregnancy, hypothyroidism, ingestion of alcohol, diabetes, or estrogen exposure.
Patients may exhibit eruptive xanthoma, lipemia retinalis, hepato-splenomegaly and may have recurrent episodes of abdominal pain and acute pancreatitis.
It is caused by extremely high levels of triglycerides, which collectively is caused by the buildup of large lipoprotein particles (chylomicrons) that are critical to the transport of dietary fats in the circulation.
Persistent chylomicronemia is characterized by extremely high fasting triglyceride levels of more than 880 mg/dL reflecting the marked accumulation of chylomicron particles owing to impaired lipolytic clearance.
Lipoprotein apheresis can greatly lower elevated triglyceride levels in the short term.
Management includes restriction of total fat intake to less than 10-15% of daily calories, which is often ineffective in preventing chylomicronemia and acute pancreatitis.
Apolipoprotein C- III elevated plasma levels are a major risk factor for hypertriglyceridemia.
Volanesorsen lower is triglyceride levels to less than 750 mg/dL in 77% of patients with familial chylomicronemia syndrome (Witztum J).
In patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and lower incidence of pancreatitis than those who received placebo (PALISADE study group).
Treatment with olezarsen leads to significant reductions in triglyceride levels and incidence of acute pancreatitis.