Case Studies| Volume 13, ISSUE 3, P411-414, May 2019

Atypical familial dysbetalipoproteinemia associated with high polygenic cholesterol and triglyceride scores treated with ezetimibe and evolocumab

Published:March 06, 2019DOI:


      • A case of familial dysbetalipoproteinemia presented with severe hyperlipidemia.
      • No obvious clinical or laboratory secondary stimulus for elevated lipids was found.
      • Genetic analysis found APOE E2/E2 and high polygenic risk scores for lipid traits.
      • Statin intolerance led to successful treatment with ezetimibe and evolocumab.


      We present a 37-year-old man diagnosed with familial dysbetalipoproteinemia who presented with the severe hyperlipidemic phenotype. None of the usual metabolic triggers were found to explain his severe lipid abnormalities. Genetic analysis revealed the expected APOE E2/E2 genotype, but no other mutations were found to explain any monogenic dyslipidemia or syndrome. Polygenic risk scores for quantitative lipid traits did reveal scores placing the patient in the >99th percentile for the general population concerning polygenic susceptibility for both high cholesterol and triglycerides. Owing to his gastrointestinal intolerance to two high-intensity statins, he was treated with both ezetimibe 10 mg a day and evolocumab 140 mg subcutaneously every 2 weeks. All measures of potentially atherogenic lipids were markedly improved and remained so for more than 10 months of follow-up. This case report shows an unusual trigger for severe hyperlipidemia with familial dysbetalipoproteinemia and a favorable therapeutic response to the combination of ezetimibe and evolocumab.


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