ORAI1基因缺陷性联合免疫缺陷病一例并文献复习

摘要

Objective To summarize the clinical manifestations and gene variations of combined immunodeficiency caused by ORAI1 variation with a case report and literature review.Methods The clinical data of the patient who was diagnosed with ORAI1 variation caused combined immunodeficiency in the Department of Pediatrics in Xiangya Hospital of Central South University in February 2018 were extracted and analyzed.The literature till August 2018 was searched with key words of'ORAI1',and 'immunodeficiency'in both English and Chinese in the database of China national knowledge infrastructure (CNKI),Wanfang and Pubmed.Results The patient was a 15 months old girl with acute onset of bilateral ptosis after upper respiratory tract infection,which was rapidly progressed to systemic myasthenia and accompanied with recurrent respiratory tract infection during the treatment.The patient poorly to responded immunomodulatory therapy and anti-infection therapy.Laboratory tests demonstrated decreased complement C3 and NK cell (CD3-CD56+),increased anti-thyroglobulin,thyroid peroxidase antibody and B lymphocyte (CD3-CD19+),and slightly increased anti-acetylcholine receptor antibody.Genetic analysis showed the homozygous variation of ORAI1 gene exon 1 c.12 G＞T (p.E4D),with heterozygostty of both parents.There were only 4 papers reporting this disease in the literature review.A total of 7 patients with ORAI1 gene variation were reported,including 3 homozygous variations,2 heterozygous variations and 2 complex heterozygous variations.The clinical manifestations included early onset recurrent infection,congenital hypotonia,elevated serum IgA and IgM,decreased NK cells,and family history of hereditary diseases.Four of the 7 reported cases died of pulmonary infection and sepsis,and the other 3 survived with low muscular tone and poor self-care ability.Conclusions The most common clinical manifestations of ORAI1 variation caused combined immunodeficiency are recurrent infection and congenital hypotonia.Myasthenia induced recurrent respiratory tract infection is an important factor of poor prognosis in severe patients.There is a lack of effective treatment for this disease,and the prognosis is poor.%目的 报道1例ORAI1缺陷性联合免疫缺陷病,并结合文献对该病临床特征及治疗预后进行探讨.方法 对中南大学湘雅医院儿科2018年2月诊治的1例ORAI1基因变异患儿的临床资料进行分析.以“ORAI1””免疫缺陷”“immunodeficiency”为关键词,对中国知网数据库、万方数据知识服务平台、Pubmed数据库建库至2018年8月收录的文献进行检索,总结该病临床特征、治疗及预后.结果 患儿女,1岁3月龄起病,临床表现为上呼吸道感染后双侧眼睑下垂,急性病程,很快进展出现全身肌无力症状、治疗期间出现反复呼吸道感染,免疫治疗和抗感染治疗效果欠佳;实验室检查补体C3降低,抗甲状腺球蛋白升高,甲状腺过氧化物酶抗体升高,抗乙酰胆碱受体抗体轻度升高,B淋巴细胞(CD3-CD19+)升高,NK细胞(CD3-CD56+)降低;基因检测发现ORAI1c.12(exon 1)G＞T(p.E4D)纯合变异,其父母为杂合变异.文献检索共收集相关病例报道4篇(均为英文),共报道7例ORAI1基因变异患者,其中纯合变异3例、杂合变异2例、复合杂合变异2例,临床表现为早期发作的复发性感染,先天性肌张力减退,血清IgA、IgM升高,NK细胞数减少,都具有家族遗传病史等,该病预后较差,7例患儿中4例死于肺部感染、脓毒症,另外3例虽然存活,但仍然肌张力低下,生活不能自理.结论 ORAI1缺陷性联合免疫缺陷病患儿临床上常表现为反复感染、先天性肌张力减退等症状,呼吸肌无力致反复呼吸道感染等是重症患者以及患儿预后不良的重要因素.该病缺乏有效治疗手段,预后较差.