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

Familial Hypercholesterolemia (FH) 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 FH and sitosterolemia. The proband was diagnosed initially as FH, 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*). NGS re-sequence for FH genes revealed an APOB heterozygous functional variant (c.11477C>T/p.(Thr3826Met), in a region previously unstudied. The mother presented the same genotype. Control of LDL-C levels was only accomplished with dietary and therapeutic intervention for both sitosterolemia and FH. The correct diagnosis of dyslipidemia is important to establish proper dietary and pharmacological intervention for atherosclerosis prevention.