X-连锁无丙种球蛋白血症临床分析及基因诊断

Clinical analysis and genetic diagnosis of X-linked agammaglobulinemia

目的分析X-连锁无丙种球蛋白血症(XLA)的临床特点及Bruton酪氨酸激酶(BTK)的基因突变情况。方法回顾分析通过基因检测确诊的20例XLA患儿的临床资料,以及采用Sanger测序方法分析BTK基因的突变情况。结果 20例患儿均为男性,发病年龄6～54月龄,平均(26.3±14.61)月龄;基因诊断确诊年龄26～168月龄,平均(64.7±38.22)月龄;诊断周期中位数为27.5月龄(3～114月龄)。临床表现以呼吸道感染为主,其中18例诊断为肺炎,另外2例为消化道感染。免疫功能检测示成熟B淋巴细胞缺如或比例显著降低,血清IgG、IgA及IgM水平明显降低。基因检测提示错义突变10例,无义突变4例,移码突变3例,内含子剪切位点突变2例,剪接突变1例。20例患儿明确诊断后均给予静脉输注丙种球蛋白替代治疗,感染频次均显著减少,均无后遗症。结论对反复严重、特殊部位感染的男童,尤其是有相关家族史的患儿,尽早行免疫功能筛查,并行基因检测明确诊断及遗传咨询。

Objective To analyze the clinical features of X-linked agammaglobulinemia (XLA) and the gene mutation of Bruton tyrosine kinase (BTK). Method The clinical data of 20 children with XLA confirmed by genetic testing were retrospectively analyzed, and the mutation of BTK gene was analyzed by Sanger sequencing. Results All the 20 cases were male, and the age at onset was from 6 to 54 months, and an average age was 26.3±14.61 months. The age at gene diagnosis was from 26 to 168 months and an average age was 64.7±38.22 months. The median diagnostic period was 27.5 months (3~114 months). Respiratory tract infection was the main clinical manifestation of all cases: 18 cases were diagnosed of pneumonia and the other 2 cases were diagnosed of digestive tract infection. Immune function test showed that either mature B lymphocytes were absent or the proportion of mature B lymphocytes was significantly reduced, and serum IgG, IgA and IgM levels were significantly reduced. Gene detection revealed 10 missense mutations, 4 nonsense mutations, 3 frameshift mutations, 2 intron shear site mutation and 1 splicing mutation. Twenty patients were received intravenous gamma globulin replacement therapy after the diagnosis, and the frequency of infection was significantly reduced without sequelae. Conclusion For boys with recurrent severe and special site infection, especially those with related family history, immune function screening should be performed as soon as possible, along with genetic testing, for clear diagnosis and genetic counseling.