Tyk2基因突变致原发性免疫缺陷病1例报告并文献复习

Tyk2 gene mutations in primary immunodeficiency disease:a case report and literature review

目的探讨Tyk2基因突变致原发性免疫缺陷病的临床特点及诊断要点。方法回顾性分析中国首例Tyk2基因突变致原发性免疫缺陷病患者的临床资料,并复习相关文献。结果患儿,男,1岁3个月。临床表现为反复肺部感染,慢性中耳炎,顽固性湿疹样皮疹,反复皮肤脓肿,单纯疱疹病毒(HSV)感染,胞内菌感染,总Ig E明显升高;Tyk2基因检测为16号外显子c.2269 C>G和3号外显子c.149 delC杂合突变复合杂合突变。文献检索到其他8例Tyk2基因缺陷致免疫缺陷患儿,男5例、女3例,均为Tyk2基因纯合突变;均发生反复鼻窦、肺部感染,其中伴结核分枝杆菌感染6例,反复病毒感染4例,脑膜脑炎4例,顽固性湿疹样皮疹3例,沙门杆菌肠炎2例;总Ig E显著升高1例,嗜酸性粒细胞明显增多1例;5例患儿来自于近亲结婚家庭;1例已死于不明病原所致的脑膜脑炎。结论当反复鼻窦、肺部感染、合并胞内菌感染(包括结核杆菌感染)、反复病毒感染或顽固性湿疹样皮疹、伴或不伴总Ig E升高,需考虑Tyk2基因缺陷致免疫缺陷病可能,基因序列分析可协助早期诊断。

Objective To explore the clinical features and diagnosis of primary immunodefciency disease caused by Tyk2 gene mutations. Methods Clinical data from the frst case in China diagnosed of primary immunodefciency disease caused by Tyk2 gene mutation were retrospectively analyzed, and related literature was reviewed. Results One year and 3 month old boy suffered with repeated pulmonary infection, chronic otitis media, intractable eczema like rash, repeated skin abscess, HSV infection, intracellular bacterial infection, and remarkedly increased total IgE. It was detected that compound heterozygous mutations of c.2269C 〉 G in No. 16 exon and c.149delC in No. 3 exon in Tyk2 gene. Literature searching found other 8 cases （5 males and 3 females） of immune defciency patients caused by Tyk2 gene defects, all of which had Tyk2 gene homozygous mutations and presented with repeated infection of paranasal sinus and lung. In the 8 cases 6 cases were combined with mycobacterium tuverculosis infection, 4 cases had repeated virus infection, 4 cases had meningonecephalitis, 3 cases had intractable eczema like rash, 2 cases had salmonella enteritis, 1 case had remarkedly increased total IgE, one case had elevated eosinophils, 5 cases were born in intermarriage family and 1 case died of meningitis caused by unknown etiology. Conclusions When patients have repeated paranasal sinus infection and lung infection, combined with intracellular bacterial infection （including mycobacterium tuberculosis infection）, and repeated virus infection or intractable eczema like rash, with or without increased total IgE, immunodefciency disease caused by Tyk2 gene defection should be considered. Gene sequence analysis can assist in early diagnosis.