BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality.
METHODS: A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn\'t improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child\'s family. Unfortunately, the child had expired due to severe infection.
CONCLUSIONS: To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality.

CGD is a rare primary immunodeficiency with high mortality rates when treated conventionally, especially for the X-chromosome-linked form. HSCT is the only curative therapy for CGD; however, haploidentical transplantation in CGD is rare. Here, we report a case of X-linked CGD treated successfully by haploidentical HSCT. The patient showed a positive result with full donor chimerism, good quality of life, and the absence of recurrent infectious diseases at follow-up (68 months). Thus, haploidentical HSCT may serve as an acceptable treatment approach for patients who have CGD, but no HLA-matched related or unrelated donor.