目的:评价3例A20单倍体功能不全(HA20)患儿的临床和遗传学特征。
方法:回顾性分析2016年8月至2019年10月在首都儿科研究所(CIP)治疗的3例HA20患儿的临床和基因检测资料。
结果:患者1表现为关节炎和炎症性肠病,患者2表现为轴性脊髓关节炎和狼疮样综合征,病人3出现复发性口腔溃疡,胃肠溃疡,和肛周脓肿.关于实验室测试,发现患者的白细胞(WBC)计数升高,C反应蛋白(CRP)和红细胞沉降率(ESR)。据报道,所有患者的CRP和ESR均较高。据报道,患者1和3的WBC较高。患者2的抗核抗体阳性,抗干燥综合征抗原A,dsDNA,类风湿因子和Coombs试验。基因检测显示3例患者均存在TNFAIP3基因杂合突变。至于治疗,患者1接受TNFα拮抗剂治疗,患者2用TNFα拮抗剂和柳氮磺胺吡啶治疗,患者3接受糖皮质激素和沙利度胺治疗。患者1和2分别随访4个月和3个月,分别。关节和胃肠道症状改善;炎症指标和类风湿因子(RF)正常,dsDNA和Coombs试验呈阴性.患者3在另一家医院接受治疗,口腔溃疡和肛周脓肿逐渐改善。
结论:HA20是由肿瘤坏死因子(TNF)-α诱导蛋白3(TNFAIP3)基因突变引起的单基因自身炎性疾病。它可能表现为Behçet样综合征,也类似于各种其他自身免疫性疾病。皮质类固醇和免疫抑制剂是有效的治疗方法,和细胞因子拮抗剂可用于难治性病例。对于早发或Behçet样综合征患儿应积极进行全外显子组基因检测,以实现早期诊断和准确治疗。
OBJECTIVE: To evaluate the clinical and genetic characteristics of 3 children with Haploinsufficiency of A20 (HA20).
METHODS: The clinical and genetic testing data of 3 children with HA20 treated at Capital Institute of Pediatrics (CIP) between August 2016 and October 2019 were retrospectively analysed.
RESULTS: Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. Regarding laboratory tests, patients were found to have elevated white blood cell (WBC) count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The CRP and ESR was reported to be high in all the patients. The WBC was reported to be high in patient 1 and 3. Patient 2 was positive for antinuclear antibodies, anti-Sjögren\'s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene. As for the treatment, patient 1 was treated with TNFα antagonist, patient 2 was treated with TNF α antagonist and sulfasalazine, and patient 3 was treated with corticosteroids and thalidomide. Patients 1 and 2 were followed for four and 3 months, respectively. There was an improvement in joint and gastrointestinal symptoms; inflammatory indices and rheumatoid factor (RF) were normal, and dsDNA and Coombs test became negative. Patient 3 was treated at another hospital and showed gradual improvement in oral ulcers and perianal abscesses.
CONCLUSIONS: HA20 is a single-gene auto-inflammatory disease caused by mutation in tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene. It may present as Behçet-like syndrome and resemble various other autoimmune diseases as well. Corticosteroids and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with early-age onset or Behçet-like syndrome to achieve early diagnosis and accurate treatment.