Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis.

Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive lipid disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis. Because the disorder is often misdiagnosed or not diagnosed and because traditional triglyceride lowering medications are often ineffective, the disease leads to a tremendous physical, social and emotional burden on afflicted patients and their caretakers. Mutations in 5 different genes have been implicated in the development of FCS, all of which have an effect on the activity of lipoprotein lipase. Lipoprotein lipase(LPL) is responsible for removing triglycerides from chylomicrons and other triglyceride rich lipoproteins in the circulation, breaking them down into free fatty acids for use as energy. Patients with FCS have loss of function of their LPL leading to severely elevated chylomicrons in the circulation and hence, severe hypertriglyceridemia. The principle treatment for FCS is to reduce chylomicron formation in the gut by placing the patient on an extremely low fat diet. New medications in development hold significant promise for improving the quality of life for FCS patients.

Extreme hypertriglyceridemia: Genetic diversity, pancreatitis, pregnancy, and prevalence.

BACKGROUND: Triglyceride (TG) concentrations >2000 mg/dL are extremely elevated and increase the risk of pancreatitis. OBJECTIVES: We characterized five cases and two kindreds and ascertained prevalence in a reference laboratory population. METHODS: Plasma lipids and DNA sequences of LPL, GPIHBP1, APOA5, APOC2, and LMF1 were determined in cases and two kindreds. Hypertriglyceridemia prevalence was assessed in 440,240 subjects. RESULTS: Case 1 (female, age 28 years) had TG concentrations >2000 mg/dL and pancreatitis since infancy. She responded to diet and medium-chain triglycerides, but not medications. During two pregnancies, she required plasma exchange for TG control. She was a compound heterozygote for a p.G236Gfs*15 deletion and a p.G215E missense mutation at LPL, as was one sister with hypertriglyceridemia and pancreatitis during pregnancy. Her father was heterozygous for the deletion and had hypertriglyceridemia and recurrent pancreatitis. Other family members had either the missense mutation or the deletion, and had hypertriglyceridemia but no pancreatitis. In kindred 2, three preschool children had severe hypertriglyceridemia and were homozygous for a GPIHBP1 p.T108R missense mutation. Case 5 (male, age 43 years) presented with pancreatitis and TG levels >5000 mg/dL and had heterozygous GPIHBP1 p.G175R and APOC2 intron 2-4G>C mutations. On diet, fenofibrate, fish oil, and atorvastatin, his TG concentration was 2526 mg/dL, but normalized to <100 mg/dL with added pioglitazone. In our population study, 60 subjects (0.014%) of 440,240 had TG concentrations >2000 mg/dL, and 66.7% were diabetic and had elevated insulin levels. CONCLUSIONS: Extreme hypertriglyceridemia is rare (0.014%); and during pregnancy, it may require plasma exchange.