The Challenges of Diagnosing Familial Dysbetalipoproteinemia: A Case Associated With a Rare ApoE Variant.

Abstract

Familial dysbetalipoproteinemia (FDB) is a lipid disorder characterized by defective clearance of triglyceride-rich lipoprotein remnants. Definitive diagnosis has relied on genetic markers, lipid profiles, and specialized lipid assays including gel electrophoresis that demonstrates the characteristic beta-band consistent with enriched small VLDL and IDL. We present a case of a 51-year-old female with progressive hyperlipidemia despite a stable plant-based diet and regular exercise. Her lipid profile met many of the diagnostic criteria for FDB (ApoB < 120 mgd/L, TG > 133 mg/dL [1.5 mmol/L], and TG/ApoB ratio < 8.8). However, advanced lipid testing failed to demonstrate hallmark lipid remnant accumulation, likely due to statin therapy initiation prior to the time of testing. Genetic testing revealed heterozygosity for the ApoE2 variant (Arg176Cys) and another novel variant of unknown significance (VUS), 593 G > A (Arg198His), on the same allele (herein termed ApoE2-Wolverine). The ApoE2-Wolverine variant may be contributing to the patient's dyslipidemia; however, further investigation into its functional significance and cardiovascular implications is needed. Her treatment with rosuvastatin 10 mg, 2 g of daily eicosapentaenoic acid (EPA), and lifestyle modifications contributed to improvements in her lipid levels. This case highlights the diagnostic challenges in FDB, especially when novel genetic variants are involved. While many criteria for FDB were met, confirmatory gel electrophoresis and genetic testing were inconclusive. This case underscores the need for multimodal assessment in FDB diagnosis, incorporating genetic analysis, lipid profiles, and therapeutic response.