A 16 years old female presented with anemia requiring repeated transfusion since last 4 years. No significant past or family history. On examination she had severe pallor and splenomegaly(14cm). Laboratory investigation showed anemia(5.5gm/dl) with thrombocytopenia(12,000/cumm), mild indirect hyperbilirubinemia (Total bilirubin: 2.41mg/dl , Direct bilirubin: 0.71mg/dl) and reticulocytosis (18.63%). Peripheral smear showed numerous stomatocytes with giant platelets and polychromatophilic cells. Manual platelet count were 60,000-75,000/cumm. Lipid profile were within normal range. Direct Coombs test was negative. In view of hemolytic anemia and peripheral smear finding, sitosterolemia was suspected. Next generation sequencing (NGS) showed mutation in the ABCG5 with homozygous for c.727 C>T, confirmed the diagnosis of sitosterolemia. Ezetimibe drug was prescribed. Patient in regular follow-up and showed significant improvement with hemoglobin. 

Sitosterolemia is a rare autosomal recessive disorder is caused by mutations in the ABCG gene. Mutations in the ABCG5 or ABCG8 gene causes defective sterolin transporter and impair the elimination of plant sterols and cholesterol from the body. These fatty substances accumulate in the arteries, skin, and other tissues, resulting in xanthomas, atherosclerosis and the additional signs and symptoms of sitosterolemia. Excess plant sterols, such as sitosterol, in red blood cells likely make their cell membranes stiff and prone to rupture, leading to hemolytic anemia. Changes in the lipid composition of the membranes of red blood cells and platelets may account for formation of stomatocytes and macrothrombocytpenia [1].

Ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1 (NPC1L1. It reduces the gastrointestinal absorption of plant sterols, thereby also lowering the serum concentrations of plant sterols. This pharmacological property of ezetimibe shows its potential as a novel effective therapy for sitosterolemia[2].

References:

1. Zhaoyue Wang  Lijuan Cao  Yanhua Su  Gaifeng Wang  Ruijuan Wang  Ziqiang Yu  Xia Bai  Changgeng Ruan, Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia, American Journal of hematology, 26 October 2013.

2. Tsubakio-Yamamoto K, Nishida M, Nakagawa-Toyama Y, Masuda D, Ohama T, Yamashita S. Current therapy for patients with sitosterolemia: effect of ezetimibe on plant sterol metabolism. J Atheroscler Thromb. 2010;17:891–900