X-连锁淋巴细胞异常增生症4例临床特点与基因突变分析

Clinical features and gene mutation analysis of 4 Chinese children with X-linked lymphoproliferative disease

目的总结X-连锁淋巴细胞异常增生症（XLP）病例的临床特点、基因突变及其家系特点等。方法回顾性总结2010年9月至2013年6月在北京儿童医院诊治的4例XLP患儿的临床资料，检测6类免疫缺陷基因突变位点，并回顾文献。结果4例患儿均为〈5岁男童，以发热起病。入院后予更营洛韦抗病毒、血浆、丙种球蛋白营养支持、激素抑制炎性反应等治疗，其中3例患儿呈暴发性或致死性传染性单核细胞增多症（FIM）表现，终死于EB病毒（EBV）相关噬血细胞淋巴组织细胞增生症（HLH），发病后的生存时间为20d左右；1例合并EBV相关HLH、药物超敏反应综合征，经治疗好转出院。2例有兄弟、表兄弟夭折家族史。4例患儿EBV-CAIgM、EBVDNA均呈阳性，且DNA拷贝数均〉108拷贝／L。经6类免疫缺陷基因DNA序列测定分析均明确有SH2D1A基因突变，但位点不同。其中3例患儿的母亲均为与患儿相同的SH2D1A基因突变携带者。结论XLP男童在婴幼儿发病，多有家族史，临床上常表现为FIM，易并发HLH，表现为SH2D1A基因突变，预后差。临床上怀疑者应尽早行免疫缺陷基因突变分析检查，早诊早治。

Objective To summarize clinical, gene mutation and their families of 4 Chinese children with X- linked lymphoproliferative （XLP） disease. Methods The clinical records and 6 genes of immunodefieiency associated with Epstein-Barr（EBV） infection were summarized and the literatures were reviewed. Results The four cases were all boys younger than 3 years old, who had onset with fever. They were all treated with ganciclovir, plasma,intravenous im- munoglobulin and methylprednisolone after hospitalization, but 3 cases had the features of fulminant or fatal infectious mononucleosis （ FIM ） ,whose progression of disease was getting worse and died of second hemophagoeytic lymphohistio- eytosis （HLH） in the end. The survival time after onset was about 20 days. One boy had the complications of HLH as- sociated with EBV infection and drug-induced hypersensitivity syndrome, who was improved and discharged from hospi- tal. Two cases had adverse family history in which brothers or cousins died at younger ages. EBV-CAIgM and EBV-DNA of the 4 cases were all positive,with the copy of EBV DNA 〉 108 eopies/L. The results of the 6 genes of immunodefi- ciency associated with EBV infection of the 4 boys showed SH2D1A mutation. Mothers of 3 cases separately had the same SH2DIA mutation as her boy, while 1 mother refused to have the genes detected. Conclusions Patients who had the XLP were all male. Infants and young children under 5 years old usually had the features of FIM ,with the complica- tion of EBV associated HLH. Patients with XLP showed SH2D1A mutation. For male patients with FIM, especially those under 5 years,it is important to perform genetic detection early and to receive therapy as early as possible.