谷固醇血症的临床特征及生化和基因诊断

Clinical features and biochemical and genetic diagnosis in patients with sitosterolemia

目的对谷固醇血症患儿的临床特征及生化和基因检测结果进行分析,以提高临床对该病的认识和诊疗水平。方法对2016年11月至2021年6月,因皮肤黄瘤病伴高胆固醇血症来复旦大学附属儿科医院就诊的4例患儿,回顾其临床特征及常规生化检测结果,并采用气相色谱-质谱联用技术测定患儿血清中的植物固醇谱。采用全外显子测序方法,分析其致病基因,对所发现的ABCG5基因变异,采用Sanger测序方法进一步验证。结果4例患儿中,男性2例,女性2例,年龄为15月龄~10岁6月。患儿关节伸侧面等处皮肤有线样或结节状多发黄色瘤,血总胆固醇均高于正常。4例患儿的菜油固醇为129.83~325.37μmol/L(正常范围0.01~17.96μmol/L),豆固醇为23.54~40.10μmol/L(正常范围0.01~10.25μmol/L),谷固醇为152.49~531.71μmol/L(正常范围0.01~15.44μmol/L)。4例患儿的基因检测结果提示均为ABCG5基因的复合杂合变异,共检出6种不同的变异类型。结论谷固醇血症患儿以关节附近皮肤皱褶处的黄色瘤为主要表现,常规生化提示血胆固醇升高,建议完善血清植物固醇谱分析并结合基因测序,以便尽早饮食指导和药物干预,改善预后。

Objective To analyze the clinical characteristics and biochemical and genetic diagnosis of patients with sitosterolemia,then to improve the level of clinical diagnosis and treatment.Methods Four cases of children presented with multiple xanthomas and hypercholesterolemia during November 2016 to June 2021 in Children's Hospital of Fudan University were included.The clinical manifestations,laboratory examinations were retrospectively analyzed.Serum phytosterol profiles were measured by gas chromatography-mass spectrometry.DNA was extracted from peripheral blood and analyzed with whole exome sequencing(WES).Sanger sequencing method was used to verify the ABCG5 gene mutation and parental source.Results Four cases of children including 2 boys and 2 girls presented with multiple linear and intertriginous xanthomas around skin of the joint extensor side at the age from 15 months to 10 years and 6 months.Skin linear or nodular xanthomatosis were found on the extensional side of joint.Total cholesterol of these 4 cases was elevated.The campesterol level was 129.83-325.37μmol/L(0.01-17.96μmol/L),the stigmasterol level was 23.54-40.10μmol/L(0.01-10.25μmol/L),and the sitosterol level was 152.49-531.71μmol/L(0.01-15.44μmol/L).The results of genetic analysis showed that 4 cases carried compound heterozygous variants in ABCG5 gene,and 6 different mutation types were detected.Conclusions Children with sitosterolemia present with skin xanthoma around the joint areas.Routine biochemistry indicates that blood cholesterol is elevated.Serum phytosterol profiles detection and genetic analysis should be carried out as early as possible,so as to provide early dietary guidance and drug intervention,and improve the prognosis.