A case report of neonatal-onset chronic granulomatosis disease with aspergillus infection and literature review

Abstract

Objective \nTo study the clinical features, diagnosis, treatment and genetic characteristics of chronic granulomatosis disease (CGD) in neonates, and to improve the understanding of CGD. \n \n \nMethod \nClinical manifestations and treatments of one patient with CGD and aspergillus infection in our hospital were analyzed. Key words including infant , newborn , chronic granulomatous disease , lung abscess , and aspergillus infection were searched in Chinese medical databases, PubMed and Embase until 2018 September. The clinical features and genetic mutations of CGD reported in literature were summarized. \n \n \nResult \nThe patient in our hospital was a full-term male infant naturally delivered with birth weight of 3 400 g. The onset of the disease was on the 19th day after birth, and the initial clinical manifestations included fever, cough, and then pulmonary abscess, diarrhea, recurrent skin infection, and aspergillus infection. Anti-infection and symptom-alleviating treatments were not effective, and weight gain was poor. Laboratory examination indicated bacterial and fungal infection. The neutrophil respiratory burst test was positive and indicated CGD. Hetero-zygotic frameshift mutation [c.1599-1602delAGTT (p.V534Sfs*12)] of CYBB gene 13 exon was detected and the diagnosis of CGD was confirmed. The mother carried the heterozygous mutation and the father didn′t. Antifungal therapy was continued after the children got better and discharged from hospital. The patient was followed up until 3-month-old and his condition was stable. Our literature review revealed 28 reports including 108 cases of CGD infants, including 79 male cases (73.1%) and 21 female cases (19.4%). Most of the CGD infants (79/108, 73.1%) had the onset within 2 weeks of life. The main clinical features included pneumonia/pulmonary abscess/pleural effusion (87.0%), diarrhea (58.3%), perianal abscess (35.2%), skin infection (53.7%), aspergillus infection (41.7%), and tuberculosis infection (26.9%). 75 cases had positive neutrophil respiratory burst test (69.4%), and 95 cases were diagnosed using genetic tests (88.0%). Over 300 loci of the CYBB gene mutation had been reported contributing to the disease. 28 cases had abnormal family history (25.9%), 19 cases received hematopoietic stem cell transplantation (17.6%), 41 cases had clinical improvement (38.0%), and 35 cases died (32.4%). \n \n \nConclusion \nCGD is rare in neonatal period. The main clinical manifestations included recurrent infection with pathogens like aspergillus, tuberculosis and others. CGD can be diagnosed based on recurrent multiple bacterial or fungal infections, neutrophil respiratory burst test and gene tests. CGD should be considered among children with recurrent infections at early life stage, especial1y those with poor maternal history or positive family history. \n \n \nKey words: \nGranulomatous disease, chronic;\xa0Lung abscess;\xa0Aspergillus;\xa0Infant, newborn