Sitosterolemia misdiagnosed as homozygous familial hypercholesterolemia: A diagnostic challenge

Sitosterolemia is a rare genetic disease caused by loss of function homozygous or compound heterozygous mutations in either ABCG5 or ABCG8 genes encoding sterols transporters. The net effect leads to an increase in sterols intestinal absorption and a reduction in sterols bile excretion causing sterols accumulation in plasma and tissues. The spectrum of clinical manifestations is variable and sitosterolemia is often misdiagnosed as familial hypercholesterolemia, particularly in patients with tendon or tuberous xanthomas. However, the triad of hematologic abnormalities, good response to ezetimibe therapy and poor response to statins should raise the suspiscion for sitosterolemia. The diagnosis is based on high plasma sterols (sitosterol and campesterol) -the hallmark laboratory feature of sitosterolemia- and confirmed by genetic analysis. The combination of dietary approach and ezetimibe therapy represents the mainstay treatment of sitosterolemia patients. Lipoprotein apheresis could be used as adjunctive therapy. This case illustrates a stepwise approach for the diagnosis of sitosterolemia and summarizes the pathophysiology, clinical presentations and management of sitosterolemia. It raises sitosterolemia awareness among physicians for an early diagnosis and appropriate therapeutic approach.