[X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia: report of a family and literature review].

Objective: To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'. He had suffered from recurrent upper respiratory tract infection and sinusitis previously. Hemoglobin level was 38 g/L. The absolute count of reticulocytes was 223.2×10(9)/L. Urobilinogen level was 38 μmol/L (3-16 μmol/L). Coomb's test was positive. Both total (77.2 μmol/L) and indirect bilirubin (66 μmol/L) levels were elevated. There was an inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger brother mainly suffered from recurrent upper respiratory tract infection, accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio and number of total B cells (45.7%). A total of 7 reports were retrieved including 11 male cases caused by MAGT1 gene mutation. These 11 cases were characterized by EBV viremia (11 cases), recurrent upper respiratory tract infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8 cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune thrombocytopenia or hemolytic anemia (2 cases). Conclusion: XMEN often manifests as male onset, recurrent upper respiratory tract infection, otitis media or sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune diseases and reduction of CD4(+)/CD8 (+)T cell ratio. NKG2D expression in NK cells is significantly reduced, and gene sequencing analysis shows a pathogenic mutation in MAGT1 gene.目的： 探讨X连锁镁离子通道缺陷原发性免疫缺陷病（XMEN）的临床特征及基因突变特点。 方法： 回顾性分析深圳市儿童医院风湿免疫科2016年8月诊治的XMEN一家系中2例患儿的临床资料、免疫学指标及基因突变特点。以MAGT1基因或XMEN为检索词，检索PubMed、万方、中国知网、重庆维普2010年1月至2017年3月MAGT1基因突变相关文献。总结XMEN患者的临床特征、免疫学指标及基因突变特点。 结果： 先证者男，2岁8月龄，因"发现尿色加深2 d，皮肤黄染1 d"入院。既往有反复上呼吸道感染及鼻窦炎病史。辅助检查：血红蛋白38 g/L；网织红细胞绝对值223.2×10(9)/L；尿胆原38 μmol/L(3~16 μmol/L)；Coomb试验：间接抗人球蛋白试验（+），直接抗人球蛋白试验（++++）；总胆红素77.2 μmol/L，间接胆红素66 μmol/L；CD4(+)/CD8(+)T细胞比值0.89；基因测序分析显示MAGT1基因3号外显子c.472delG、p.D158Mfs*6移码突变。先证者弟弟1岁6月龄，亦存在反复上呼吸道感染、CD4(+)/CD8(+)T细胞比值（0.45）降低、B细胞占淋巴细胞总数比例(45.7%)及绝对计数(3 894/μl)增加、MAGT1基因3号外显子c.472delG、p.D158Mfs*6移码突变。2例患儿NK细胞NKG2D表达均显著降低。文献检索共收集7篇英文文献，共包括11例男性XMEN患者，均存在MAGT1基因突变，其中EB病毒血症11例，反复上呼吸道感染、中耳炎或鼻窦炎10例，继发肿瘤性疾病8例，CD4(+)/CD8(+)T细胞比值（<1）降低7例，免疫性血小板减少或溶血性贫血2例。 结论： XMEN主要临床特征包括男性发病、反复上呼吸道感染、中耳炎或鼻窦炎、EB病毒血症、淋巴增殖性疾病或淋巴瘤、自身免疫性疾病、CD4(+)/CD8(+)T细胞比值降低及NK细胞NKG2D表达显著减少，基因测序分析显示MAGT1基因存在致病性变异。.