From Bernard-Soulier syndrome to sitosterolemia: the role of genetic analysis in bleeding diathesis

Bleeding diathesis' diagnosis can be challenging due to the high number of disorders with hemorrhagic symptomatology. Sitosterolemia is a rare disease characterized by increased sterols plasma levels and cardiovascular, cutaneous, articular, and hematological manifestations, including anemia and macrothrombocytopenia. The disorder is caused by ABCG5 and ABCG8 mutations.We present a case of a patient with bleeding diathesis, macrothrombocytopenia, a moderate defect of primary hemostasis and a pathological platelet aggregation analysis, with an initial diagnosis of Bernard-Soulier variant syndrome. After performing a genetic study using an exome analysis, the patient had two ABCG8 gen variants, one pathogenic (NP_071882.1:p.Trp536Ter (NM_022437.2:c.1608G > A) variant, ClinVar ID: 499930) and the other one probably pathogenic (NP_071882.1:p.Leu465Arg (NM_022437.2:c.1394T > G) variant), changing the diagnosis to sitosterolemia, which has its own therapeutic approach.This case report shows the importance of the genetic analysis. Sitosterolemia should be suspected in the presence of macrothrombocytopenia, stomatocytes in the blood smear and hemolytic anemia, performing a genetic study including ABCG5 and ABCG8 gene variants.