Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematological abnormalities of sitosterolemia.


Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PS) usually produce xanthomas and premature coronary atherosclerosis, although hematological abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis.


To report two novel ABCG5 gene variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL.


A 46-year-old female was referred to us presenting life-long macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed by high-throughput sequencing. Plasma PS levels were evaluated by gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974 reports.


A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of the ABCG5 gene. The patient displayed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematological abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematological abnormalities.


This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. Definitive diagnosis of STSL by measurement of serum PS and molecular analyses prompted the use of ezetimibe therapy. This article is protected by copyright. All rights reserved.

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