Gestational hyperlipidemic pancreatitis caused by type III hyperlipoproteinemia with apolipoprotein E2/E2 homozygote.

To the Editor: Gestational hyperlipidemic pancreatitis is an uncommon but serious disorder. In women having type I, IV, or V hyperlipoproteinemia (HLP), the superimposition of the physiologic hyperlipidemia of pregnancy may lead to acute pancreatitis. Here, we present a case of gestational hyperlipidemic pancreatitis associated with apo E2/E2 homozygous type III HLP. A 39-year-old gravida 3, para 2 woman without known medical history except hyperlipidemia for 3 years and regular medication until 6 months before preparation of gestationwas referred to our hospital for acute pancreatitis at 14 weeks of gestation. On arrival, the lipid profiles showed hypercholesterolemia (807 mg/dL) and hypertriglyceridemia (3596 mg/dL). During her stay in the hospital, she received total parenteral nutrition for 14 days and resumed oral intake with low-fat diet smoothly. She was discharged at 18weeks of gestation and continued with the low-fat diet with fish oil supplement (4 g/d) according to the dietitian’s instruction. She gave birth to a healthy male infant at 39weeks of gestation, and her triglyceride level fell below 1000 mg/dL after delivery. At 25 weeks of gestation, the patient, her family (except her mother who died of lymphoma), and a normal control subject underwent laboratory screening. Serum lipoprotein analyses by agarose gel electrophoresis from the patient, her father and elder brother showed broad A-very low-density lipoprotein (VLDL) bands (Fig. 1A), suggestive of type III HLP. The results of apo E genotype with direct sequencing showed that the patient had apo E2/E2 genotype in which thymidine replaced the normally occurring cytosine at base pair 3883 (Fig. 1B). Her father and elder brother had apo E2/E3 genotype. The rest of her family and the normal control subject had apo E3/E3 genotype (data not shown). The association of pregnancy, hypertriglyceridemia, and acute pancreatitis is well established. To our knowledge, the case described in this letter is the first case of apo E2/E2 homozygous familial type III HLP-related gestational hyperlipidemic pancreatitis. Type III HLP is an inborn error of metabolism characterized by defective apo E, which is a ligand for the receptormediated uptake of chylomicron and VLDL remnants by the liver. More than 90% of type III HLP subjects are homozygous carriers of apo E2 (Arg158 Y Cys), which displays less than 1% binding affinity for the cell surface lipoprotein receptors. However, less than 10% of apo E2/E2 homozygous subjects have hyperlipidemia. These observations indicate that other genetic environmental factors or concomitant diseases are necessary for expression of the hyperlipidemia in apo E2/E2 subjects. In our case, pregnancy is very likely to play the role for expression of the extremely high levels of plasma triglyceride and cholesterol. The fish oil is well known to decrease VLDL secretion from the liver and thus lower the production of intermediatedensity lipoproteins and low-density lipoprotein. A dose of 3 to 4 g n-3 fatty acids per day decreases serum triglyceride levels by around 30% to 50% in hypertriglyceridemic patients. Thus, fish oil supplement could be an effective therapy for prevention of gestational hyperlipidemic pancreatitis. In summary, we report a pregnant patient with apo E2/E2 homozygous familial type III HLP-related hyperlipidemic pancreatitis at 14 weeks of gestation. She received total parental nutrition and then low-fat diet during hospitalization, continued low-fat diet and fish oil supplement in outpatient clinic, and gave birth to a healthy male infant at 39 weeks of gestation.