**Background:** Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency of phagocytes caused by defects in the NADPH oxidase complex, leading to recurrent bacterial and fungal infections and hyper-inflammatory manifestations. The disease can be X-linked (XL-CGD, due to CYBB mutations) or autosomal recessive (AR-CGD, due to mutations in CYBA, NCF1, NCF2, or NCF4). Data on CGD in Egypt are limited. This study aimed to describe the clinical presentations, infectious and non-infectious features, and outcomes of a large Egyptian CGD cohort over 10 years.
**Methods:** This retrospective study was conducted at the Pediatric Department of Cairo University Children's Hospital from 2011 to 2021. It included 173 patients with confirmed CGD diagnosis based on dihydrorhodamine (DHR) assay by flow cytometry. Intracellular staining of neutrophil NADPH components (gp91phox, p22phox, p47phox, p67phox) was performed for 160 patients. Targeted Sanger sequencing was done for 44 patients. Clinical data, microbiological workup, vaccination history, and outcomes were recorded. Statistical analysis used SPSS, with p<0.05 considered significant.
**Key Results:** Of 173 patients (107 males, 66 females), AR-CGD was diagnosed in 132 (76.3%): 83 (48%) with p47phox defect, 44 (25.4%) with p22phox defect, and 5 (2.9%) with p67phox defect. XL-CGD was diagnosed in 25 (14.4%). Sixteen patients (9.2%) could not be categorized. Positive consanguinity was reported in 141 (81.5%) patients, with 91.7% among AR-CGD. Median age at diagnosis was 48 months (range 1-186 months), and median age at presentation was 7 months (range 0.2-180 months). The most common first manifestation was pneumonia, followed by skin and lymph node abscesses. Overall, deep-seated abscesses and pneumonia were the most frequent clinical manifestations. Gram-negative bacteria (53.8%) were more common than gram-positive (46.2%) among 91 bacterial infection episodes; Staphylococcus species (37/91) and Klebsiella species (18/91) were most frequent. Aspergillus species were the most common fungal infections (38/58, 65.5%), followed by Candida species (17/58, 29.3%). Mycobacterial infections occurred in 44 episodes: Mycobacterium tuberculosis (24/44, 54.5%), BCG (13/44, 29.5%), and atypical mycobacteria (7/44, 16%). Regional BCG-itis was recorded in 13 patients (7.8%). Non-infectious manifestations included granuloma (17 patients), IBD (9 patients), arthritis (4 patients), and vasculitis (3 patients). Regarding outcome, 36 patients (20.8%) were lost to follow-up. Among 137 patients with known outcome, 94 (68.6%) are living and 43 (31.4%) died. Pneumonia was the most common cause of death (32/43, 74.4%). Comparing AR and XL groups, XL patients had earlier age of onset (p=0.029), but no significant difference in mortality. Among subgroups, p47phox-deficient patients had the highest DHR stimulation index (p=0.007), highest age at presentation (p=0.001), and longest overall survival (p=0.001). p22phox-deficient patients had the highest mortality (50%), while p47phox-deficient patients had the lowest (18.7%).
**Clinical Implications:** This study confirms the predominance of AR-CGD in Egypt, driven by high consanguinity rates. The delayed diagnosis (median 48 months) and low number of patients undergoing hematopoietic stem cell transplantation (only 6 patients) underscore the need for early diagnosis and improved management. The high incidence of mycobacterial infections, including tuberculosis and BCG complications, suggests that CGD should be ruled out in any patient presenting with typical or atypical mycobacterial disease. The emergence of drug-resistant bacterial species (25.2% of bacterial isolates) highlights the importance of antimicrobial stewardship. The significant differences in outcomes among genetic subgroups (e.g., better survival in p47phox deficiency) may guide prognosis and counseling. Genetic counseling and prenatal diagnosis were offered to families, with 4 families seeking prenatal diagnosis.