自身免疫性淋巴细胞增殖综合征1例家系分析并文献复习  

Autoimmune lymphoproliferative syndrome:analysis of 1 pedigree and review of literature

作　　者：刘江华 刘炜[1] 李彦格 Liu Jianghua;Liu Wei;Li Yange(Department of Hematology and Oncology,Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital,Zhengzhou Children's Hospital,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属儿童医院、河南省儿童医院、郑州儿童医院血液肿瘤科,郑州450000

出　　处：《白血病．淋巴瘤》2022年第12期738-741,共4页Journal of Leukemia & Lymphoma

基　　金：河南省医学科技攻关项目(LHGJ20190918)。

摘　　要：目的提高对自身免疫性淋巴细胞增殖综合征(ALPS)的认识。方法回顾性分析郑州大学附属儿童医院2018年8月收治的1例ALPS先证者及其家系成员的临床资料,提取患儿及其父母、胞兄、胞姐的外周血DNA,采用高通量二代测序进行基因检测,分析其表型及基因型,并进行文献复习。结果先证者为1岁1个月男性患儿,以溶血性贫血、血小板减少、脾大为主要临床表现,双阴性T细胞、维生素B12明显升高,自身抗体阳性。患儿父亲有脾大史,患儿胞兄、胞姐具有与患儿类似的临床表现。二代测序结果示患儿及其父亲、胞兄、胞姐均检测出FAS基因移码突变(c.648delT),为新发突变。患儿经免疫抑制治疗后症状好转,血细胞上升。结论FAS基因移码突变可能为该ALPS家系患者的致病原因。临床上对不明原因的血细胞减少、肝脾大患者,需考虑ALPS可能,应行双阴性T细胞、自身抗体、维生素B12等检测,必要时行高通量基因测序。Objective To improve the understanding of autoimmune lymphoproliferative syndrome(ALPS).Methods The clinical data of the proband and his family members in Children's Hospital Affiliated to Zhengzhou University in August 2018 were retrospectively analyzed,and the peripheral blood DNA of the proband,his parents and siblings was extracted.High-throughput next-generation sequencing was used to make gene analysis and validation.Phenotype and genotype of them were also analyzed.Relevant literature was reviewed.Results The proband was a 1-year and 1-month old boy with hemolytic anemia,thrombocytopenia and splenomegaly as the main manifestations.The double negative T cells and the Vitamin B12 of the proband were significantly increased and the autoantibodies were positive.The boy's father had a history of splenomegaly.His elder brother and sister had similar clinical manifestations.The results of next-generation sequencing showed that the FAS gene frameshift mutation(c.648delT)was detected in this boy and his father,elder brother and sister,which was a new mutation.After immunosuppressive treatment,the symptoms of the boy improved and the blood cells increased.Conclusions The frameshift mutation of FAS gene may be the cause of the disease in this ALPS pedigree.Clinically,it is necessary to consider ALPS for children with unexplained hemocytopenia and hepatosplenomegaly.Double-negative T cells,autoantibodies,Vitamin B12 should be tested,and high-throughput gene sequencing should be performed if necessary.

关 键 词：自身免疫性淋巴细胞增殖综合征 FAS基因 诊断 治疗 

分 类 号：R725.5[医药卫生—儿科]