Title:Sitosterolemia: Diagnosis, Metabolic and Hematological Abnormalities, Cardiovascular Disease and Management
Volume: 26
Issue: 37
关键词:
血小板疾病，谷固醇，大血小板减少症，高通量核苷酸测序，基因检测，高胆固醇血症。
摘要: Sitosterolemia is a recessive inherited metabolic disorder of unknown prevalence,
characterized by increased levels of plasma plant sterols. It is caused by 28 and 31 variants in
ABCG5 and ABCG8 genes, respectively, and is characterized by a predisposition to hyperabsorption
and accumulation of toxic levels of plant sterols in plasma. Its clinical picture is extremely
heterogeneous. The main clinical features are tendinous and cutaneous xanthomas, arthritis
or arthralgia, premature cardiovascular disease and atherosclerosis. These characteristics
are shared with familial hypercholesterolemia (FH), making it possible for sitosterolemia to be
misdiagnosed as homozygous FH, especially in pediatric patients. In such cases, a specific
chromatography-based laboratory method is essential to differentiate sitosterol and cholesterol.
Hematological abnormalities (hemolytic anemia and macrothrombocytopenia) may be present in
25-35% of patients, in whom it is usually associated with the main clinical features, as occurs in
the 70% of the cases. In this context, the peripheral blood smear is essential and reveals giant
platelets and stomatocytes. Only 21 causative variants in ABCG5/ABCG8 are associated with
macrothrombocytopenia. Most physicians still do not recognize these hematological abnormalities
or relate them to sitosterolemia. Patients may suffer long-term misdiagnosis of immune
thrombocytopenia and be at high risk of receiving harmful therapies or of not benefitting from a
low-cholesterol diet and/or from the gold standard treatment with ezetimibe. This drug reduces
the levels of plasma plant sterols, provokes regression of xanthomas, and can alleviate hematological
abnormalities. Finally, to identify genetic defects, recent advances in high-throughput
sequencing, especially in the use of targeted sequencing of pre-specified genes, have begun to be
incorporated in the first-line approach in the field of genetic disorders.
