Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Ann Allergy Asthma Immunol. 2016 Oct;117(4):405-411. doi: 10.1016/j.anai.2016.07.044. Epub 2016 Sep 1.
X-linked agammaglobulinemia (XLA) is an X-linked genetic defect in maturation of B lymphocytes that results in the absence of B lymphocytes in the peripheral blood and profound hypogammaglobulinemia. It is caused by a mutation in the BTK gene located on the X chromosome. There are no large series describing XLA from the developing world.
To analyze the clinical features, immunologic and genetic characteristics, and outcomes of 36 patients with XLA diagnosed and managed for a period of 2 decades.
Diagnosis of XLA was made on the basis of presence of BTK gene mutation or marked reduction of B lymphocytes in peripheral blood with a family history of an affected male relative. The diagnosis was confirmed by genetic mutation studies in 28 patients with 25 unique mutations in the BTK gene.
There was a significant delay in diagnosis in most of the patients. The mean (SD) delay in the diagnosis was 4.2 (3.5) years. Point mutations were the most common mutations detected, accounting for 68% of all mutations. Deletions and insertions were also seen in a few cases. Four of the mutations are novel mutations that have not been previously reported. Seven of the 36 patients (19%) were dead at the time of analysis in the present cohort. The mean survival was 137 months (95% confidence interval, 13-163 months).
The present study is perhaps the largest series of patients with XLA from any developing country so far.
X 连锁无丙种球蛋白血症(XLA)是一种 X 连锁遗传缺陷,导致 B 淋巴细胞成熟障碍,外周血 B 淋巴细胞缺失,伴严重低丙种球蛋白血症。其病因是位于 X 染色体上的 BTK 基因突变所致。目前尚无来自发展中国家的关于 XLA 的大型系列研究。
分析 36 例 XLA 患者的临床特征、免疫和遗传特征及预后,这些患者接受诊断和治疗的时间跨度为 20 年。
根据存在 BTK 基因突变或外周血 B 淋巴细胞显著减少,伴男性受累亲属的家族史,诊断 XLA。在 28 例患者中,通过基因突变为 25 种独特的 BTK 基因突变证实了诊断。
大多数患者的诊断存在显著延迟,平均(标准差)延迟诊断时间为 4.2(3.5)年。点突变是最常见的突变类型,占所有突变的 68%。少数病例还存在缺失和插入。其中 4 种突变是以前未报道过的新突变。在本队列中分析时,36 例患者中有 7 例(19%)死亡。平均生存时间为 137 个月(95%置信区间,13-163 个月)。
本研究可能是迄今为止来自任何发展中国家的最大系列 XLA 患者研究。