新生儿X-连锁慢性肉芽肿病4例分析暨文献复习

Four cases of neonatal X-linked chronic granulomatous disease and literature review

目的了解X-连锁慢性肉芽肿病（X-CGD）患儿的临床特点、治疗方法及基因突变类型。方法选择我科2013年4-12月经基因检测明确诊断为X-CGD的病例,总结患儿起病时间、症状、影像学表现、病原学检查、治疗及转归情况,了解基因突变类型。结果研究期间共收治4例X-CGD患儿,均为男婴,起病日龄13~17天,诊断日龄24-34天,1例有家族史。首发症状发热3例,咳嗽1例。肺CT表现为结节、不规则、球形或类圆形高密度灶。痰培养1例为烟曲霉菌和金黄色葡萄球菌,1例为白色念珠菌,2例阴性;血培养均阴性;血清半乳甘露聚糖（GM）试验阳性3例。应用抗细菌联合抗真菌治疗2-3周,4例均好转出院,随访6个月3例未复发,1例出院后未按医嘱服药生后5个月因反复严重感染死亡。CYBB基因突变分析示缺失突变1例,插入突变1例,错义突变2例,患儿母亲均为携带者。结论本病在新生儿期呼吸道症状及体征相对较轻,但影像学显示肺部病变严重,肺CT表现为多发结节或团块影,常规体液和细胞免疫功能正常的新生儿应考虑X-CGD。CYBB基因突变分布广泛,异质性明显,基因突变分析将成为产前诊断的重要工具。

Objective To investigate clinical features, treatments and genetic mutations in children with X-linked recessive granulomatous disease （X-CGD）. Methods This retrospective study analyzed clinical data of patients with genetically confirmed diagnosis of X-CGD between April to December of 2012 at Beijing Children＇ s Hospital. Data review was conducted on the age of onset of symptoms, clinical presentations, imaging findings, DNA testing results, treatment options, outcomes and types of genetic mutations. Results All four cases were boys, with age of symptom onset at 13-17 days old and diagnosis at 24-34 days old. One case had family history. Theinitial presenting symptom was fever in three cases and cough in one case. Chest CT revealed pulmonary nodulesor high-density lesions that were irregular; spherical or oval shaped. While the blood culture was negative for all four patients, sputum culture was positive for two patients： one with Aspergillus fumigatus ＆ Staphylococcus aureus, the other with Candida albicans. Serum galactomannan （GM） test was positive in 3 cases. After anti- bacterial and anti-fungal treatments, all patients were improved anddischarged. Three patients haveremained symptom free for 6 months, however, one patient died of recurrent severe infection at 5 months of age due to non-compliance. CYBB gene mutation analysis revealed one case of deletion, one case of insertion, and two cases ofmis-sense mutations. All four babies inherited their CYBB mutation from their carrier mother. Conclusions Althoughpatients with X-CGD usually presented with mild respiratory symptoms during neonatal period, marked abnormal findings were found on imaging studies. Findings ofmultiple nodules or mass lesions on Chest CT with normal humoral and cellular immune functions should lead to the clinical suspicion of X-CGD. CYBB mutations are widely distributed with heterogeneity. Therefore, mutational analysis of genes should become an important tool for prenatal diagnosis of X-CGD,