儿童腺苷脱氨酶2缺乏症2例并文献复习

Two cases of adenosine deaminase 2 deficiency in children and literature review

目的总结2例腺苷脱氨酶2(ADA2)缺乏症患儿的临床表型及基因特点,并进行文献复习,提高对该病的认识。方法对2019年3月至12月就诊于青岛大学附属医院的2例ADA2缺乏症患儿的临床资料和基因型进行分析。查阅国内外数据库相关文献,总结该病的临床特征及基因变异特点。结果1.本组2例患儿均存在ADA2基因突变,例1表现为反复发热、网状青斑、结节性多动脉炎及免疫缺陷,为ADA2基因c.571delC(p.Q191Sfs*5)纯合突变,国内外均未见报道,为新发变异;例2表现为反复发热、脂膜炎、下肢血管炎及免疫缺陷,为ADA2基因c.1358A>G(p.Y453C)纯合突变,该位点在国内尚未见报道。2.国外基因确诊患儿共171例,国内仅报道3例,加上本研究2例国内共5例,该5例主要临床表现反复发热(5/5例),皮肤网状青斑(4/5例),脂膜炎(1/5例),皮肤坏疽(1/5例),生长迟缓(1/5例),脑梗死(3/5例),体液免疫缺陷(4/5例),血液系统受累(3/5例),肌痛(2/5例),炎性指标C反应蛋白、红细胞沉降率升高(5/5例)。结论ADA2缺乏症临床表现多样,掌握其临床特点,有助于提高临床诊治水平。c.571delC突变位点国内外均未见报道,为新发现的ADA2基因突变类型,进一步丰富了ADA2基因谱。

Objective To summarize the clinical phenotype and genotype features of 2 children with adenosine deaminase 2(ADA2)deficiency,and to review the related literature so as to enhance the understanding of this disease.Methods The phenotype and genotype of 2 cases with ADA2 deficiency who visited the Affiliated Hospital of Qingdao University from March to December 2019 were analyzed.Literature was searched from foreign and domestic databases and studied to summarize clinical and gene mutation characteristics of children with ADA2 deficiency.Results(1)ADA2 gene mutation was found in both children.One case was characterized by recurrent fever,livedo reticularis,polyarteritis nodosa and immunodeficiency.The mutation site c.571delC(p.Q191Sfs*5)of the ADA2 gene detected in this case was a homozygous mutation,which was a new mutation point and not reported in China or abroad previously.The other case was characterized by recurrent fever,panniculitis,vasculitis with legs,and immunodeficiency.The mutation site c.1358A>G(p.Y453C)was a homozygous mutation that was not reported in China previously.(2)There were 171 cases of children diagnosed with ADA2 deficiency in foreign countries,but only 5 cases(3 previously reported cases and 2 cases in this study)were detected in China.The main clinical phenotypes were recurrent fever(5/5 cases),livedo reticularis(4/5 cases),panniculitis(1/5 cases),cutaneous gangrene(1/5 cases),growth retardation(1/5 cases),cerebral infarction(3/5 cases),humoral immunodeficiency(4/5 cases),blood system involvement(3/5 cases),and myalgia(2/5 cases),elevated inflammatory markers(C-reactive protein,erythrocyte sedimentation rate)(5/5 cases).Conclusions Children with ADA2 deficiency have various clinical phenotypes,and a good understanding of phenotypes can improve the level of clinical diagnosis and treatment.The mutation point of c.571delC is a novel ADA2 gene mutation type,which further enriches the ADA2 gene spectrum.