戈谢病GBA基因突变致血小板输注无效1例

Platelet transfusion refractoriness caused by GBA gene mutation in one patient with Gaucher disease

目的分析1例血小板输注无效患者及其家系戈谢病葡萄糖脑苷脂酶(GBA)基因突变特征。方法 1例贫血及血小板减少的女性患者经血小板输注无效后,对其进行骨髓细胞学、B超及基因测序检测;采用干血斑法检测其白细胞β-葡糖脑苷脂酶活性;提取该家系8个成员(包括先证者及其直系亲属)外周血基因组DNA进行基因测序。结果骨髓细胞学检查示该例患者可见戈谢细胞(6.0%),白细胞β-葡糖脑苷脂酶活性为3.78 nmol/(h·mgPro),B超结果示脾肿大;基因测序分析发现其为GBA基因c.484A>G纯合错义突变;家系调查结果表明,先证者父母、子女及妹妹5人均为GBA基因杂合突变。结论戈谢病患者可因脾功能亢进而出现血小板输注无效;GBA基因突变为该家系的主要致病因素。

Objective To analyze the mutation characteristics of GBA gene in one patient with Gaucher disease and platelet transfusion refractoriness. Methods A female patient with anemia and thrombocytopenia showed platelet transfusion refractoriness, and then the proband and her family were performed bone marrow smear, β-glucocerebrosidase activity in leukocytes （ dried blood spot assay）, β- ultrasonography and gene sequencing examination and pedigree investigation. Results Pedigree investigation showed that the heterozy- gous mutation of GBA gene existed in the father, mother, son, daughter and sister of the proband. Bone marrow cytomorphologic exami- nation showed that Gaucher cells accounted for 6.0% in the female patient. The β-glucocerebrosidase activity in leukocytes was 3.78 nmol/（h · mg Pro）. B-ultrasonography showed slightly splenomegaty. Gene sequencing found that the homozygous mutation of GBA gene, c. 484A 〉 G, existed in the female patient. Conclusion The patients with Gaucher disease may appear platelet transfusion re- fractoriness due to hypersplenism. The mutation of GBA gene is the main pathogenic factor of the family with Gancher disease.