In November 2018, an 8-month-old boy was hospitalized due to fever and cough for 10 days. Even though the patient was susceptible to upper respiratory tract infections, he had no history of severe infectious diseases nor was he allergic to food or drugs. The patient was born at term with no complications. His family history revealed that his maternal uncle died early in infancy due to pneumonia; the patient's brother was 4 years old and healthy. On admission, the patient underwent physical examination; a few moist rales were observed in both lungs. Laboratory findings showed high IgE and IgA levels (Table 1). Test results for complement levels, complete blood count, and mitogen-induced T-cells were normal. Neutrophil phagocytosis assays revealed that the patient's peripheral blood neutrophils presented impaired phagocytotic functions (Fig. 1). After PMA stimulation, only 4.65% of the patient neutrophils could devour APC beads while in the other samples, normal phagocytosis was observed in >20% neutrophils. Serological tests did not reveal infection with human immunodeficiency virus and he was antibody-negative for some common viruses, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), and other herpes viruses. Additionally, the patient tested negative for Mycobacterium tuberculosis and Mycoplasmal pneumonia by pharyngeal swab antigen test and cultures. High resolution computed tomography (HRCT) revealed multiple patchy infiltrating shadows and a diffuse consolidation with air bronchograms on admission (Fig. 2). His condition deteriorated rapidly after admission to the hospital, quickly progressing to respiratory failure, shock, and organ dysfunction and failure. He died three days after admission despite being administered anti-infective therapy (vancomycin and meropenem) and all intensive care (transfusion, mechanical ventilation, and continuous blood purification). After his death, sputum and blood cultures yielded multiple drug-resistant Burkholderia cepacia, whereas microscopic examination of the transbronchial lung biopsy (TBLB) revealed Aspergillus hyphae.
The family tree of the patient (Fig. 3A) includes three generations with a total of eight people. The proband has been diagnosed with X-linked CGD. Apart from his uncle's death in infancy because of pneumonia, others have no history of recurrent or severe respiratory infection. The proband detected a novel mutation on the CYBB gene in the patient, a G deletion in locus c.1234 on the CYBB gene of X chromosome (c.1234delG) (Fig. 3B). This mutation shifts valine to serine at residue 413 creating a premature stop codon (p. V413Sfs*22). Besides, the same mutation was detected on one of the X chromosomes of his mother, aunt, and grandmother, who we called carriers. However, no CYBB gene mutation was detected in the infant's father, his other uncle or his brother. Thus, it was clear that the mutated gene came from his mother who inherited it from his grandmother.