X连锁无丙种球蛋白血症患儿4例及相关文献分析

4 cases of X-linked agammaglobulinemia and related literature analysis:case report and literature review

目的综合运用个例研究及Meta分析的方法,探讨X连锁无丙种球蛋白血症(XLA)的临床表现、诊断以及与Bruton酪氨酸激酶(BTK)基因表型之间的关系,以加强临床医师对该疾病的认识。方法①回顾性分析于西安市儿童医院确诊的4例XLA患者的临床特点;②通过万方、知网、Pubmed数据库对XLA相关文章进行检索,按照一定的纳入排除标准对检索结果进行筛选及Meta分析。结果共纳入文献44篇,XLA患者共202例,所收集的XLA患者病例中均经基因分析确诊。202例XLA患者临床表现中呼吸道感染最常受累,为177例(87.6%),其次为中耳炎、关节炎、消化道感染、鼻窦炎、中枢神经感染、皮肤感染、败血症等,其中有15例(7.4%)合并有自身免疫性疾病。BTK基因突变类型包括错义突变87例(43.1%)、移码突变49例(24.3%)、无义突变33例(16.3%)、剪接突变26例(12.9%)和缺失突变7例(3.5%)。3~6岁XLA患儿的基因突变类型不同,差异有统计学意义(χ^2=10.849,P<0.05),临床表现为神经性耳聋的XLA患者基因突变类型以缺失突变为主,具有统计学意义(Pfisher<0.05)。文献中有明确结构区基因突变的共142例,其中TK占46.5%、PH占25.4%、SH2占14.1%、SH3占11.3%、TH占2.8%,XLA患者临床表现为泌尿系统受累与不同结构区基因突变具有相关性(Pfisher<0.05)。结论 XLA的临床表现多种多样,以反复感染最为常见,XLA患者BTK基因突变类型以错义突变最为多见,突变结构区以TK、PH最为多见,临床表现为神经性耳聋的XLA患者基因突变类型以缺失突变为主,且XLA患者临床表现为泌尿系统受累与不同结构区基因突变具有相关性。

Objective To investigate clinical manifestation,diagnosis of X-linked agammaglobulinemia(XLA) and relationship of XLA with Bruton tyrosine kinase(BTK) gene phenotype with a combination of case study and meta-analysis to enhance clinicians’ understanding of the disease.Methods ①The clinical characteristics of 4 cases of XLA diagnosed in Xi’an Municipal Children’s Hospital were retrospectively analyzed.②The papers related to XLA were retrieved through wanfang,cnki and Pubmed databases,and the results were screened and meta-analyzed according to certain inclusion and exclusion criteria.Results A total of 44 reference literature were enrolled,including 202 patients with XLA,all of whom were confirmed by genetic analysis.Among the clinical manifestations of 202 patients with XLA,respiratory tract infection was the most frequent,accounting for 87.6%(177 cases),followed by otitis media,arthritis,digestive tract infection,sinusitis,central nervous system infection,skin infection and septicemia in order,among which 15 cases(7.4%) complicated with autoimmune diseases.The types of BTK mutation included missense mutations in 87 cases(43.1%),transcoding mutations in 49 cases(24.3%),nonsense mutations in 33 cases(16.3%),splicing mutations in 26 cases(12.9%) and deletion mutations in 7 cases(3.5%).The genetic mutation type of XLA children in ≤3-year age group and that in ≤6-year age group was different,and the difference was significant(χ^2=10.849,P<0.05),and the type of gene mutation of XLA patients whose clinical manifestations was nervous deafness was mainly missing mutations,the difference was statistically significant(Pfisher<0.05).In the literature,there were 142 cases of gene mutations with defined structural regions,among which TK accounted for 46.5%,PH for 25.4%,SH2 for 14.1%,SH3 for 11.3% and TH for 2.8%.The urinary system involvement in clinical manifestations of XLA patients was correlated with gene mutations in different structural regions(Pfisher<0.05).Conclusion The clinical manifestations of XLA patients are diverse,among which repeated infections are most common.Missense mutations are the most common type of BTK gene mutation,and TK and PH are the most common mutated structural regions.The main gene mutation type of XLA patients with nervous deafness is deletion mutation,and urinary system involvement of XLA patients is correlated with gene mutations in different structural regions.