PIK3CD基因突变致PI3Kδ过度活化综合征1例并文献复习

doi:10.6040/j.issn.1671-7554.0.2020.1386

摘要/Abstract

摘要： 目的探讨PI3Kδ过度活化综合征(APDS)的临床表现、基因突变特征及治疗方法。方法回顾性分析确诊的1例APDS患儿的临床资料,并进行文献复习,总结其临床表现、基因突变特点及治疗预后。结果患儿,女,9岁,因“反复咳嗽8年,腹泻3年,肝功异常2年”入院;胸腹部CT:右肺中叶部分肺组织膨胀不全,其内支气管扩张,肝大,脾大,腹腔、腹膜后、盆腔多发肿大淋巴结;CD4+/CD8+倒置,IgG正常,IgM升高,基因结果:PIK3CD基因杂合突变c.3061G>A(p.E1021K),确诊为APDS1;予以免疫球蛋白替代及雷帕霉素口服治疗,随访1年2个月后,肝、脾及淋巴结明显缩小,大便正常,未再出现反复呼吸道感染;以“PI3Kδ过度活化综合征”“激活P13Kδ综合征”为关键词检索万方医学及中国知网数据库,以“activated phosphoinositide 3-kinase δ syndrome”“activated PI3Kδ syndrome” “PIK3CD”“PIK3R1”“APDS”为关键词检索Pubmed数据库,目前中外共报道285例,其中国内报道42例,加上本例共43例,仅1例为APSD2型;与国外报道相比,我国APDS患者支气管扩张及高IgM的发生率更高,尚无合并恶性肿瘤的报道。APDS1型热点突变是c.3061 G>A(p. E1021K),APDS2型热点突变为c.1425+1 G>(A, C, T)(p.434-475del)。结论 APDS是一种罕见的以抗体缺陷为主的原发性免疫缺陷病,多表现为反复呼吸道感染、支气管扩张、非肿瘤性淋巴组织增生、慢性腹泻、自身免疫性疾病、恶性肿瘤、发育延迟、免疫学检查CD4+/CD8+倒置、高IgM、IgG具有多变性;免疫球蛋白替代治疗能减少感染机会,雷帕霉素可改善肝、脾和淋巴结肿大,造血干细胞移植效果良好。

关键词: PI3Kδ过度活化综合征, 免疫缺陷病, 基因突变, 反复呼吸道感染, 支气管扩张

Abstract: Objective To explore the clinical features, gene mutations and treatment in patient with activated phosphoinositide 3-kinase δ syndrome(APDS). Methods The data of one patient who was diagnosed as APDS were retrospectively analyzed,and the related literatures were reviewed. The clinical features, gene mutations and treatment were summarized. Results The patient, a 9-year old Chinese girl, was hospitalized in Shandong Provincial Hospital Affiliated to Shandong First Medical University because of “recurrent cough for eight years, chronic diarrhea for three years and abnormal liver function for two years”. CT scan of the chest and abdomen demonstrated that she had hepatomegaly, splenomegaly, right middle lobe bronchiectasis and lymphoid hyperplasia, and the lung tissue in the middle lobe of the right lung was not dilated completely. The immunological features were inverted CD4+/CD8+ index, normal IgG level and increased IgM level. Sanger sequencing of PIK3CD gene confirmed a de novo mutation c.3061G>A(p.E1021K), which confirmed the diagnosis of APDS1. The child received IVIG and rapamycin treatments and experienced obvious improvement in diarrhea, lymphoproliferation, hepatomegaly, and splenomegaly. Recurrent respiratory infections were not occurred. The Wanfang Medical Database, CNKI Database and Pubmed Database were searched by keywords such as “activated phosphoinositide 3-kinase δ syndrome”“activated PI3Kδ syndrome” “PIK3CD”“PIK3R1”“APDS”. A total of 285 patients were reported all over the world, in which 43 patients were Chinese including this patient. There was only one patient with APSD2 type. Compared with the overseas patients, the incidence of bronchiectasis and higher IgM level of APDS patients in China was higher. No patients combined with malignant tumors. The hotspot mutations were c.3061 G>A(p. E1021K)in APDS1 and c.1425+1 G>(A, C, T)(p.434-475del)in APDS2, respectively. Conclusion APDS is a rare primary immunodeficiency disease characterized by antibody deficiency mainly. The patients have recurrent respiratory infections, bronchiectasis, non-neoplastic lymphoid hyperplasia, chronic diarrhea, autoimmune diseases, malignant tumor, developmental delay, CD4+/CD8+ inversion, high IgM level and variable IgG levels. IVIG can reduce respiratory tract infections and rapamycin was beneficial in the treatment of non-neoplastic lymphoproliferative. Hematopoietic stem cell transplantation can significantly improve clinical status and immune function.

Key words: Activated phosphoinositide 3-kinase δ syndrome, Immunodeficiency disease, Gene mutation, Recurrent respiratory infections, Bronchiectasis

中图分类号:

黄秀丽,刘丙菊,孙立锋. PIK3CD基因突变致PI3Kδ过度活化综合征1例并文献复习[J]. 山东大学学报 (医学版), 2021, 59(3): 107-112.

HUANG Xiuli, LIU Bingju, SUN Lifeng. Activated phosphoinositide 3-kinase δ syndrome caused by a mutation in PIK3CD gene: a case report and literature review[J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 107-112.

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