Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia

Sitosterolemia (phytosterolemia) is a rare inherited sterol storage disorder, characterized by significantly elevated plasma levels of plant sterols. The clinical features of sitosterolemia are xanthomas, premature atherosclerosis, arthritis, and, occasionally, liver function impair and hematologic abnormalities. This disorder is caused by mutations of ABCG5/ABCG8 genes. We report here the clinical, laboratory, and molecular genetic features of 13 patients with sitosterolemia from eight unrelated families who had specific hematologic problems of macrothrombocytopenia, hemolytic anemia, and splenomegaly besides the major clinical manifestations. The peripheral blood films showed some unique features: large platelets surrounded by a circle of vacuoles, and various abnormal erythrocyte shapes, especially stomatocyte. According to these distinct changes of blood cell morphology, we identified two sitosterolemia patients who lacked the classical clinical phenomena. All the patients had been misdiagnosed with immune thrombocytopenia (ITP), Evans syndrome, or secondary ITP with delay being 28.8 years between symptom onset and correct diagnosis. These results indicate that sitosterolemia is certainly not as rare as originally thought. The phenomena of macrothrombocytopenia/hemolysis might represent a new platelet disorder. Plasma plant sterols and ABCG5/ABCG8 genes should be analyzed when such hematologic abnormalities are unexplained.