Gestational hyperlipidemia and acute pancreatitis with underlying partial lipoprotein lipase deficiency and apolipoprotein E3/E2 genotype
A 28-year-old female patient presented to the hospital at 21 weeks of her second pregnancy. Her weight and height were 75 kg and 163 cm, respectively. She exhibited no clinical signs suggestive of hyperlipidemia such as tendon xanthomata, eruptive xanthomata, or other skin lesions. According to her family history, her mother had diabetes mellitus, and her father also had diabetes mellitus with hyperlipidemia. Her first pregnancy 1 year prior was influenced by gestational diabetes mellitus (GDM) and severe hyperlipidemia. Her first pregnancy progressed uneventfully, and other antenatal obstetrical examinations throughout her pregnancy were within normal limits. Labor was induced at the 38 weeks of gestation, and a healthy male infant weighing 4,050 g was delivered.\nDuring the laboratory examination of her first pregnancy, functional tests of her liver, kidney, and thyroid were normal. At gestational week 25, she underwent a 50-g oral glucose tolerance test (OGTT) for screening of GDM; after 1 hour, her plasma glucose was 198 mg/dL. Next, 100-g OGTT was administered to the patient, and her plasma glucose levels at 0, 1, 2, and 3 hours were 79, 145, 175, and 169 mg/dL, respectively. Therefore, GDM was diagnosed by the Carpenter and Coustan criteria. Lipid levels indicated that her total cholesterol was 451 mg/dL, low density lipoprotein cholesterol (LDL-C) was 154 mg/dL, high density lipoprotein cholesterol (HDL-C) was 60 mg/dL, triglyceride was 1,128 mg/dL, and β-lipoprotein was 1,421 mg/dL. Supernatant samples exhibited a turbid, cloudy appearance. GDM and hyperlipidemia were managed by strict dietary control and the administration of omega-3 acid ethyl ester, which was started at 1 g/day. At 35 weeks of gestation, her lipid levels had increased with a cholesterol level at 622 mg/dL and triglyceride level at 3,360 mg/dL. Therefore, the omega-3 acid ethyl ester dose was doubled to 2 g/day. After delivery, the patient's medication was switched to fenofibrate (130 mg/day) at 6 weeks after delivery, her total cholesterol and triglyceride levels decreased to 195 and 413 mg/dL, respectively ().\nAt 21 weeks into her second pregnancy, extreme hyperlipidemia and GDM recurred with more severe laboratory findings. Upon administration of 100-g OGTT, her plasma glucose levels at 0, 1, 2, and 3 hours were 101, 158, 197, and 166 mg/dL, respectively. And lipid profile showed total cholesterol 693 mg/dL, LDL-C 99 mg/dL, HDL-C 42 mg/dL, triglyceride 3,108 mg/dL, β-lipoprotein 3,066 mg/dL, apo A1 188 mg/dL, and apo B 105 mg/dL, respectively. The patient was managed by strict dietary control and omega-3 acid ethyl esters at 2 g/day until labor. Her pregnancy progressed uneventfully, and labor was induced at the 38th week of gestation; a healthy male infant weighing 3,650 g was delivered. On the following day, she complained of epigastric pain. Peripheral blood tests showed that her cholesterol level was 1,137 mg/dL, triglyceride level was 6,600 mg/dL, amylase level was 179 U/mL (compared with normal ranges, 25 to 115), and lipase level was 133 U/L (compared with normal ranges, 13 to 60). Enhanced abdominal computed tomography revealed swelling of the pancreas with adjacent fluid collection consistent with acute pancreatitis (). After 4 days of complete parenteral nutrition and fluid therapy, her amylase and lipase levels were normalized. She was discharged 7 days after labor, with improved status of lipid levels with cholesterol 489 mg/dL and triglyceride 702 mg/dL ().\nThe patient experienced recurrent severe hyperlipoproteinemia limited to the gestational period. We performed lipoprotein electrophoresis, apoE genotyping and LPL gene analysis. Furthermore, we measured postheparin plasma LPL activity to elucidate the underlying etiology of the extreme gestational hyperlipidemia. Lipoprotein electrophoresis showed the increase of pre-β region and the decrease of β region (), and her apoE genotype was E3/2. We evaluated the LPL gene on chromosome 8q22, and detected no gene mutation. This test analyzed the entire exon, and the adjacent intron of the LPL gene was amplified using polymerase chain reaction (Model 9700, Applied Biosystems, Foster City, CA, USA), with direct gene sequencing using an automatic nucleotide sequencer (ABI 3130xl, Applied Biosystems). LPL activity was measured using an LPL enzyme-linked immunosorbent assay kit (American Diagnostica GmbH, Mannheim, Germany), performed in her nonpregnant state. A blood sample was collected from the patient after overnight fasting, and an intravascular injection of heparin was given (30 U/kg), with 5 mL of postheparin blood samples obtained 15 minutes after the injection []. LPL in samples was trapped on the plate due to the antigen-antibody reaction with the antibovine milk LPL mouse monoclonal antibody (anti-LPL monoclonal antibody) that was coated on the plate. Subsequently, antibovine milk LPL chicken serum (anti-LPL serum) was added, with horseradish peroxidase-labeled antichicken immunoglobulin G goat serum (enzyme-labeled antibody) applied to initiate the antigen-antibody reactions in each sample. The substrate o-phenylenediamine was then added for color development. The absorbance of the developed color was measured to determine LPL levels, which indicated an LPL activity level of 152 ng/mL (compared with normal values, 164 to 284).\nAfter treatment for pancreatitis, her medication was switched to fenofibrate (130 mg/day), and her cholesterol level normalized, ranging from 130 to 200 mg/dL. In contrast, her triglyceride levels were mildly elevated, ranging from 139 to 567 mg/dL.