Dysbetalipoproteinamia: Implications for Pre-Conception, Pregnancy and Beyond

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Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis A 41-year-old Chinese woman was referred to our Lipid Disorders Clinic with an elevated total cholesterol measuring 8.7mmol and triglycerides of 10.1mmol. She denied any previous history of pancreatitis. Her past medical history otherwise, was relatively unremarkable. She had an uncomplicated pregnancy and delivery 2 years ago. Family history did not reveal premature cardiovascular disease. Our patient's mother was diagnosed with hypercholesterolemia in her 60′s. Upon examination, there was no clinical stigmata of dyslipidemia. She was normotensive but overweight with a BMI of 28kg/m2. At initial review in clinic, she was 9 weeks pregnant in an unplanned pregnancy. She unfortunately lost this pregnancy a few weeks later. Genetic testing confirmed she was homozygous for ApoE2 allele. In addition, 2 variants were identified in ApoA5 showing c.553G>T and c.-644T>C. CT coronary calcium measured zero but hepatic steatosis was noted incidentally on imaging. Objective/Purpose This case raised a few challenges. Our patient was very keen to attempt a further pregnancy following a recent miscarriage. We discussed implications of dysbetalipoproteinamia in the pre-conception setting and strategies to manage a successful pregnancy safely. We also considered the longe-term cardiovascular risk to our patient in the setting of her genetic abnormalities. Methods The most common genetic cause of dysbetalipoproteinamia is homozygosity of the ApoE variant. ApoE2 can be regarded as a normal variant but in the presence of a metabolic stress such as elevated BMI in our patient's case, this may precipitate the dysbetalipoproteinamia phenotype in a recessive manner. In addition, current literature suggests her genetic mutations in ApoA5 is likely pathogenic, increasing her risk of atherosclerosis further. Our patient's ApoB was within normal limits measuring 0.87g/L. However, in dysbetalipoproteinamia, ApoB concentrations may be lower and thereby, cannot be relied on accurately to assess cardiovascular risk. Her recent calcium score of zero is reassuring but she has been counselled regarding the increased risk of cardiovascular and peripheral artery disease with her genotype. Results Current literature surrounding management of dysbetalipoproteinamia in pregnancy is limited; however, broad principles include lowering triglyceride levels to minimize risk of acute pancreatitis which carries significant morbidity in a pregnant individual. Our patient was on a statin prior to review in the lipid disorders clinic. This was discontinued as she was planning for a future pregnancy in the short term. A multidisciplinary approach was undertaken with referral to the dietician and a dedicated pre-conception clinic. Following adoption of a low fat diet, her lipid profile improved showing total cholesterol 5.9mmol, triglycerides 4.1mmol, LDL 3.0mmol and HDL 1.0mmol. She has also been advised to minimize weight gain in future pregnancies. Conclusions This is an interesting case of a young woman who presented with asymptomatic hypertriglyceridemia and subsequently found to be homozygous for ApoE2 with additional genetic mutation in ApoA5. As her primary concern was to conceive in the near future, management has been largely conservative with dietary modification and ongoing close monitoring of her lipid profile. Beyond pregnancy, it is vital her cardiovascular health is monitored closely due to increased atherogenic potential with her genotype. Nothing to disclose.