儿童自身免疫性多内分泌腺病综合征Ⅰ型2例并文献复习

Autoimmune polyendocrinopathy syndrome typeⅠin children:two case reports and literature review

目的探讨儿童自身免疫性多内分泌腺病综合征Ⅰ型(APS-Ⅰ)临床特征及AIRE基因变异。方法回顾分析河南省儿童医院2019年5—10月收治的2例APS-Ⅰ病儿临床资料,并复习相关文献,对已报道中国儿童APS-Ⅰ临床表型及基因型进行总结。结果2例男性APS-Ⅰ病儿,病例1,12岁,3岁慢性念珠菌感染,12岁重度贫血;病例2,15岁,7岁甲状旁腺功能减退,8岁慢性念珠菌感染,15岁肾上腺皮质功能减退症和重度贫血。高通量测序提示AIRE基因变异,病例1为c.44G>A(p.R15H)和c.1036C>T(p.Q346*)杂合突变,病例2为c.38T>C(p.L13P)和c.1400+2T>C杂合突变,其中c.1036C>T(p.Q346*)和c.1400+2T>C为HGMD及ClinVar数据库未报道过的变异位点,经美国人类遗传学和基因组学医学学会(ACMG)指南评估分别为疑似致病及致病变异。2例病儿给予药物治疗后临床症状缓解。分别检索PubMed、万方和CNKI数据库,共检索到22例确诊为APS-Ⅰ中国病儿,包括本研究2例,共24例,其中15例基因诊断,有14种基因变异,无热点变异,9例临床诊断。结论新的变异位点扩大了AIRE基因变异谱,APS-Ⅰ临床表现多样,且出现时间跨度大,相关抗体及AIRE基因检测有助于疾病早期诊断,多学科诊疗提供个体化的治疗策略。

Objective To investigate the clinical characteristics and AIRE gene variation of autoimmune polyendocrinopathy syn-drome typeⅠ(APS-Ⅰ)in children.Methods The clinical data of 2 children with APS-Ⅰadmitted to He'nan Children's Hospital from May 2019 to October 2019 were reviewed and analyzed,and the related literature was reviewed to summarize the clinical pheno-types and genotypes of APS-Ⅰreported in Chinese children.Results Two male APS-Ⅰcases were identified:case 1,12 years old,chronic candida infection at 3 years old,severe anemia at 12 years old;case 2,15 years old,hypoparathyroidism at 7 years old,chronic candida infection at 8 years old,and adrenal insufficiency and severe anemia at 15 years old.High-throughput sequencing indicated AIRE gene variation in both cases:c.44G>A(p.R15H)and c.1036C>T(p.Q346*)heterozygous mutations in case 1,c.38T>C(p.L13P)and c.1400+2T>C in case 2.Among them,c.1036C>T(p.Q346*)and c.1400+2T>C were mutation sites that had not been reported in HGMD and ClinVar databases,which were respectively suspected likely pathogenic and pathogenic,according to American College of Medical Genetics and Genomics(ACMG)guidelines.The clinical symptoms of 2 children were relieved after drug treatment.By search-ing PubMed,Wanfang,and CNKI databases separately,a total of 22 children diagnosed with APS-I in China were retrieved,including 2 cases in this study,for a total of 24 cases.Among them,15 cases were diagnosed with gene mutations,14 with no hotspot mutations,and 9 cases were clinically diagnosed.Conclusion The new mutation sites expand the spectrum of AIRE gene variation.The clinical manifestations of APS-Ⅰare diverse and the occurrence time span is large.Detection of related antibodies and AIRE gene is helpful for early diagnosis of the disease,and multi-disciplinary treatment provides individualized treatment strategies.