TYK2基因突变致噬血细胞综合征1例并文献复习

TYK2 gene mutation induced hemophagocytic syndrome:a case report and literature review

目的报告1例TYK2基因复合杂合突变致EBV感染相关噬血细胞综合征,并进行文献复习,提高对该病的认识。方法回顾性分析2020年12月郑州大学附属儿童医院收治1例TYK2缺陷病儿的临床特征及基因分析结果,以“酪氨酸激酶2”“TYK2”“TYK2 deficiency”“TYK2 mutation”为关键词检索中国知网、万方、维普、迈特思创、EBSCO和PubMed数据库,检索时间从建库至2022年5月31日;对以往报道TYK2缺陷病人临床特征及基因进行总结。结果男,12岁,因“发热、皮肤黄染伴纳差”入院,主要表现为发热、黄疸、腹水、肝损害、EBV感染;基因检测发现TYK2 c.209-212delGCTT和c.1645C>T复合杂合突变;给予抗感染、抗病毒、化疗、异基因造血干细胞移植等综合治疗;造血干细胞移植1个月后疾病反复,家长放弃治疗。共检索出10篇有临床资料和基因突变分析的文献,共16例病人,临床特征主要为卡介苗接种后异常反应、反复感染(主要为胞内菌及疱疹病毒感染),部分病人可伴血清免疫球蛋白E(IgE)水平升高、湿疹、外周血嗜酸性粒细胞增多。结论TYK2缺陷病人临床表现多样且极其罕见,当病儿存在卡介苗接种后异常反应、反复胞内菌及病毒感染时需警惕本病可能。

Objective To report a case of EBV infection-associated hemophagocytic syndrome caused by compound heterozygous mutation of TYK2 gene,and to review the related literature so as to improve the understanding of this disease.Methods The clinical characteristics and genetic analysis results of a child with TYK2 deficiency admitted to Children´s Hospital Affiliated to Zhengzhou University in December 2020 were retrospectively analyzed.The keywords"tyrosine kinase 2""TYK2""TYK2 deficiency"or"TYK2 mutation"were searched in various databases,including CNKI,Wanfang,Weipu,Metastron,EBSCO and PubMed.The search time was from the establishment of the database to May 31,2022.The clinical characteristics and genes of patients with TYK2 deficiency reported in the past were summarized.Results A 12-year-old boy was admitted to hospital due to"fever,yellow skin staining and poor appetite".The main manifestations were fever,jaundice,ascites,liver injury,EBV infection.Genetic tests showed TYK2 c.209-212delGCTT and c.1645C>T complex heterozygous mutations.Comprehensive treatment such as anti-infection,anti-virus,chemotherapy and allogeneic hematopoietic stem cell transplantation was given.One month after the allogeneic hematopoietic stem cell treatment,the disease recurred and the parents gave up treatment.A total of 10 literatures with clinical data and gene mutation analysis were retrieved.A total of 16 children were found.The clinical features were mainly abnormal reactions after BCG vaccination and repeated infections(mainly intracellular bacteria and herpes virus infections).Some patients may be accompanied by elevated serum Immunoglobulin E levels,eczema,increased eosinophils in peripheral blood.Conclusion The clinical manifestations of TYK2 deficiency patients are diverse and extremely rare.It is necessary to be vigilant against the possibility of TYK2 deficiency in children with abnormal reaction after BCG vaccination and repeated intracellular bacteria and virus infection.