Luo Z Q, Ye Y Z, Liao J X, Hu Z Q
Department of Neurology, Shenzhen Children's Hospital, Shenzhen 518038, China.
Zhonghua Er Ke Za Zhi. 2021 Oct 2;59(10):876-880. doi: 10.3760/cma.j.cn112140-20210309-00191.
To summarize the clinical characteristics of children with interleukin-1 receptor associated kinase 4 (IRAK4) deficiency. The clinical data of a child with IRAK4 deficiency who was admitted to the Department of Neurology of Shenzhen Children's Hospital for several times from June 2019 to August 2020 were retrospectively analyzed. Related literature up to January 2021 with the key words "IRAK4 gene variation", and "interleukin-1 receptor-associated kinase 4 deficiency" in PubMed, CNKI, Wanfang, and CQVIP databases were searched. The clinical characteristics of this disease were summarized and analyzed. The boy was 6 years of age and had recurrent respiratory tract infections. He was improved after antibiotic treatment. His clinical manifestation included meningoencephalitis, multiple sclerosis, invasive discitis and inflammatory bone destruction. Family-based whole exome sequencing showed that the boy had a homozygous frameshift variation in the IRAK4 gene, NM_016123.3:C.540del (p.Phe180leufs*26), and both parents were heterozygous. A total of 23 cases were reported in ten English articles. Together with this case, there were 24 cases, including 13 males and 11 females. The age of onset was 8 days to 7 years. The main manifestations were recurrent invasive bacterial infection, including 11 cases with meningitis, 9 cases with and (or) septicemia, 1 case with meningitis, 1 case of salmonella infection, and 1 case with skin abscess. Only 1 case had recurrent virus infection. There were 2 patients with autoimmune diseases, 1 with autoimmune encephalitis and the other one with juvenile idiopathic arthritis. Among the 24 cases, 10 died (9 in infancy). Most of the surviving children were diagnosed early and received antibiotics preventively and intravenous immunoglobulin (IVIG). Their susceptibility to infection decreased year by year, and could be close to normal children at the age of 14 years. Among the 24 cases, 21 cases had homozygous variation of IRAK4 gene and 3 cases had complex heterozygous variation. There were 15 kinds of variation, including 9 kinds of frameshift variation, 4 kinds of nonsense variation and 2 kinds of missense variation. One candidate variation hotspot was c.877 c>T (3 cases). IRAK4 deficiency mainly manifest as recurrent and invasive bacterial infection, with meningitis or septicemia being the most common. A few patients are complicated with autoimmune diseases. The mortality rate is high in infancy, early diagnosis and treatment can avoid severe illness or death.
总结白细胞介素-1受体相关激酶4（IRAK4）缺陷患儿的临床特征。回顾性分析2019年6月至2020年8月多次入住深圳市儿童医院神经内科的1例IRAK4缺陷患儿的临床资料。检索截至2021年1月PubMed、CNKI、万方和维普数据库中关键词为“IRAK4基因变异”和“白细胞介素-1受体相关激酶4缺陷”的相关文献。总结并分析该病的临床特征。该男孩6岁，反复呼吸道感染，经抗生素治疗后好转。其临床表现包括脑膜脑炎、多发性硬化、侵袭性椎间盘炎和炎性骨质破坏。基于家系的全外显子测序显示，该男孩IRAK4基因存在纯合移码变异，NM_016123.3:C.540del（p.Phe180leufs*26），父母均为杂合子。10篇英文文献共报道23例，加上本病例共24例，其中男性13例，女性11例。发病年龄为8天至7岁。主要表现为反复侵袭性细菌感染，其中脑膜炎11例、败血症9例和（或）、脑膜炎1例、沙门氏菌感染1例、皮肤脓肿1例。仅1例有反复病毒感染。有2例自身免疫性疾病患者，1例为自身免疫性脑炎，另1例为幼年特发性关节炎。24例中，10例死亡（9例于婴儿期死亡）。大多数存活患儿早期诊断并预防性使用抗生素及静脉注射免疫球蛋白（IVIG），其感染易感性逐年下降，14岁时可接近正常儿童。24例中，21例IRAK4基因存在纯合变异，3例为复合杂合变异。变异类型有15种，包括9种移码变异、4种无义变异和2种错义变异。一个候选变异热点为c.877 c>T（3例）。IRAK4缺陷主要表现为反复侵袭性细菌感染，以脑膜炎或败血症最为常见。少数患者合并自身免疫性疾病。婴儿期死亡率高，早期诊断和治疗可避免重症或死亡。
