Yang H Y, Deng X L, Yin F, Peng J, Wu L W
Department of Pediatrics, Xiangya Hospital of Central South University; Hunan Intellectual and Developmental Disabilities Research Center, Changsha 410008, China.
Zhonghua Er Ke Za Zhi. 2019 Feb 2;57(2):142-145. doi: 10.3760/cma.j.issn.0578-1310.2019.02.015.
To summarize the clinical manifestations and gene variations of combined immunodeficiency caused by ORAI1 variation with a case report and literature review. 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 infrast ructure (CNKI), Wanfang and Pubmed. 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 l 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. 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.
通过病例报告及文献复习总结由ORAI1变异导致的联合免疫缺陷的临床表现及基因变异情况。提取并分析2018年2月在中南大学湘雅医院儿科诊断为ORAI1变异导致联合免疫缺陷患者的临床资料。在中国知网（CNKI）、万方及PubMed数据库中，以中英文关键词“ORAI1”和“免疫缺陷”检索截至2018年8月的文献。该患者为15个月大女童，上呼吸道感染后急性起病，出现双侧上睑下垂，迅速进展为全身性肌无力，治疗期间伴有反复呼吸道感染。患者对免疫调节治疗和抗感染治疗反应不佳。实验室检查显示补体C3和自然杀伤细胞（CD3(-)CD56(+)）减少，抗甲状腺球蛋白、甲状腺过氧化物酶抗体及B淋巴细胞（CD3(-)CD19(+)）增加，抗乙酰胆碱受体抗体略有增加。基因分析显示ORAI1基因外显子1 c.12 G>T（p.E4D）纯合变异，父母均为杂合子。文献复习中仅有4篇报道了该疾病。共报道7例ORAI1基因变异患者，其中3例为纯合变异，2例为杂合变异，2例为复合杂合变异。临床表现包括早发性反复感染、先天性肌张力低下、血清IgA和IgM升高、自然杀伤细胞减少以及有遗传疾病家族史。7例报道病例中有4例死于肺部感染和败血症，另外3例存活，但肌张力低，自我护理能力差。ORAI1变异导致联合免疫缺陷最常见的临床表现是反复感染和先天性肌张力低下。重症肌无力诱发的反复呼吸道感染是严重患者预后不良的重要因素。该疾病缺乏有效治疗方法，预后较差。
