新生儿期起病慢性肉芽肿病临床与基因分析

Clinical and genetic analysis of neonatal onset chronic granulomatous disease

目的分析9例新生儿期起病慢性肉芽肿病(CGD)的临床特点,探讨新生儿早期诊断CGD的线索。方法对9例新生儿期起病CGD患儿的家族史、临床表现、辅助检查、治疗及预后资料进行总结分析。结果9例患儿均为男性,起病中位日龄15 d,诊断中位日龄36 d。起病时均有发热、气促、呼吸困难,6例有咳嗽。首次检测血白细胞(11.00~30.51)×10^(9)/L,均以中性粒细胞升高为主,CRP 37.16~186.30 mg/L;肺部CT均见多发结节影及团块状高密度影。9例患儿均出现肺曲霉菌感染。2例做呼吸爆发试验均阳性。7例CYBB基因变异,1例NCF1基因变异。3例死亡,5例存活,1例失访。结论临床中遇到新生儿期起病的肺部曲霉菌感染,影像学以双肺多发结节影和团块状高密度影为主要改变时应警惕CGD。新生儿CGD最常见的变异基因是CYBB,基因可发生移码突变、错义突变、剪接突变、无义突变,基因型与临床表型的关系有待进一步探讨。

Objective The clinical characteristics of 9 cases of neonatal onset of chronic granuloma(CGD)were analyzed to explore the clues of early diagnosis of CGD.Methods The family history,clinical manifestations,auxiliary examination,treatment and prognosis of 9 patients with neonatal-onset CGD were summarized and analyzed.Results All the 9 patients were boys.The median age of onset was 15 days,and the median age of diagnosis was 36 days.At the onset of the disease,there were fever,shortness of breath and difficulty breathing,and 6 cases had coughing.In all patients,the white blood cells measured for the first time ranged from 11.00×10^(9)/L to 30.51×10^(9)/L and were characterized by elevated neutrophils.CRP levels ranged from 37.16 mg/L to 186.30 mg/L.Multiple nodules and mass high density shadows were seen in CT of the lungs.All 9 patients had pulmonary aspergillosis.Respiratory burst test was positive in 2 cases.There were 7 cases of CYBB gene variation and 1 case of NCF1 gene variation.Three patients died,5 survived and 1 lost follow-up.Conclusions In case of pulmonary aspergillosis infection in neonatal stage,we should be alert to CGD when the imaging changes mainly include multiple pulmonary node shadow and mass high density shadow.The most common variant gene of neonatal CGD is CYBB.The genotype can be frame-shifting,missense,splicing and nonsense mutations.The relationship between genotype and clinical phenotype needs to be further explored.