Department of Hematology, Hospital Universitario de Salamanca-IBSAL-USAL, Salamanca, Spain.
IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain.
J Thromb Haemost. 2017 Sep;15(9):1859-1866. doi: 10.1111/jth.13777. Epub 2017 Aug 5.
Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed. Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia. High-throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias. Accurate characterization of sitosterolemia helps us determine appropriate management.
Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results 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 ABCG5. The patient showed 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 hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions 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. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.
报道 2 例新的 ABCG5 变异导致西班牙患者发生甾醇血症（STSL），并回顾 STSL 的临床和突变特征。
患者/方法：一名 46 岁女性因终生巨血小板减少症被转介至我们处就诊。她有家族性高胆固醇血症相关性黄瘤病。采用高通量测序进行分子分析。采用气相色谱法评估血浆甾醇水平。根据特定的在线数据库和自 1974 年以来发表的所有报告，回顾 STSL 图谱。
血涂片显示巨大血小板和口形红细胞。在 ABCG5 的外显子 7（c.914C>G）和 13（c.1890delT）中检测到新的复合杂合变异。患者的血浆甾醇水平升高。这些发现支持甾醇血症的诊断。在我们的综述中，我们仅发现了 25 例无相关 STSL 患者出现血液学异常，包括巨血小板减少症。为什么只有一些患者出现血液学异常仍不清楚。
这是首例被报道和分子特征明确的西班牙 STSL 患者。血涂片存在口形红细胞强烈支持早期诊断 STSL。通过测量血清甾醇水平和分子分析明确诊断 STSL 后，提示使用依折麦布治疗。
