Uncovering dysbetalipoproteinemia in a patient initially diagnosed with familial hypercholesterolemia: The role of whole exome sequencing and longitudinal follow-up in diagnostic precision and care

We report an 18-year-old woman with severe dysbetalipoproteinemia and apolipoprotein E (ApoE) deficiency. Laboratory evaluations showed total cholesterol level: 11.76 mmol/L (454.8 mg/dL); triglyceride (TG) level: 2.90 mmol/L (256.9 mg/dL), and a low-density lipoprotein cholesterol level: 8.18 mmol/L (316.3 mg/dL). Lipoprotein electrophoresis revealed elevated very-low-density lipoprotein (VLDL) cholesterol and VLDL TGs of 5.69 mmol/L (220 mg/dL) and 1.73 mmol/L (153 mg/dL), respectively. She had severe xanthomatosis, which cleared after lipid-lowering but recurred when medications were stopped. Her lipids markedly improved and remained at cholesterol targets on both atorvastatin 40 mg and ezetimibe 10 mg a day. Whole exome sequencing showed 2 novel APOE variants, c.43 + 3delA and c.754G>T, p.(Glu252Ter), with corresponding very-low levels of plasma apolipoprotein E. Familial segregation revealed that the proband carried monogenic biallelic variants in APOE and first-degree relatives heterozygous for the APOE variants. This case report highlights an unusual form of dysbetalipoproteinemia with severe ApoE deficiency associated with early onset of clinical manifestations, elevated remnant cholesterol, and a favorable therapeutic response to a combination of statins and ezetimibe.