Chronic Granulomatous Disease Presenting as Aseptic Ascites in a 2-Year-Old Child

Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency syndrome that results from abnormal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function. This defect leads to recurrent catalase-positive bacterial and fungal infections as well as associated granuloma formation. We review the case of a 2-year-old boy who presented with ascites and fever of an unknown origin as manifestations of CGD. Cultures were negative for infection throughout his course, and CGD was suspected after identification of granulomas on peritoneal biopsy. Genetic testing revealed a novel mutation in the CYBB gene underlying his condition. This paper highlights the importance of considering CGD in the differential diagnosis of fever of unknown origin and ascites in children. 1. Introduction Chronic granulomatous disease (CGD) results from the inability of neutrophils to complete the first step of the respiratory burst pathway, generation of superoxide, with the downstream consequence of impaired microbe killing. CGD leads to recurrent and potentially lethal infections. Pneumonia is the most common infection before diagnosis (47%) [1] and occurs in the majority (79%) of patients within four years of diagnosis [2]. Lymphadenitis is the second most common infection before diagnosis (45%) [1], and subcutaneous abscess is the second most common infection that occurs within 4 years of diagnosis (43%) [2]. Other presenting infections include osteomyelitis, liver and perirectal abscesses, enteritis, and septicemia [1]. CGD can, in very rare circumstances, present with ascites [3]. The incidence of CGD is estimated to be between 1/200,000 and 1/250,000 US births [2]. Most affected individuals are male because approximately 70% of mutations are X-linked recessive; the remaining 30% of cases are autosomal recessive [1, 2, 4]. In normal individuals, inflammatory stimuli prompt nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (a lysosomal enzyme encoded on chromosome 22) to produce superoxide. Superoxide is converted to hydrogen peroxide via superoxide dismutase and then to hypochlorous acid (by myeloperoxidase), which is lethal to bacteria [5]. Individuals with CGD are able to utilize hydrogen peroxide made by microbes and convert it to hypochlorous acid to preserve microbe killing, yet catalase-positive bacteria can prevent this step by degrading the hydrogen peroxide. Thus, catalase-positive organisms such as Staphylococcus aureus are the most common microbial sources of infection; other common pathogenic organisms in patients with CGD are