Complex Phenotype of Hypercholesterolemia in a Family with Both ABCG8 and APOB Mutations

Familial hypercholesterolemia is a common genetic hypercholesterolemia caused by mutations in LDLR, APOB and PCSK9 that leads to premature atherosclerosis. Other rare disorders like sitosterolemia can present the same phenotype but have distinct therapeutic interventions. We present a case of severe hypercholesterolemia in a 5-year-old child found to have both familial hypercholesterolemia and sitosterolemia. The proband was diagnosed initially as familial hypercholesterolemia, but the lack of pathogenic variants with Sanger approach questioned this hypothesis. High levels of sitosterol established the diagnosis of sitosterolemia, genetically confirmed by an ABCG8 homozygous variant c.1974C>G/p. (Tyr658*). Next-generation sequencing re sequence for familial hypercholesterolemia genes revealed an APOB heterozygous functional variant (c.11477C>T/p. (Thr3826Met), in a region previously unstudied. The mother presented with the same genotype but a milder phenotype. Control of low-density lipoprotein cholesterol levels was only accomplished with dietary and therapeutic intervention for both sitosterolemia and familial hypercholesterolemia. The correct diagnosis of dyslipidemia is important to establish proper dietary and pharmacological intervention for atherosclerosis prevention.