First review of chronic granulomatous disease in Palestine: clinical and genetic characteristics.

BACKGROUND

Chronic granulomatous disease (CGD) is an inborn error of immunity caused by genetic defects in the nicotinamide adenine dinucleotide phosphate oxidase complex, resulting in recurrent severe infections and excessive inflammatory responses. CGD is inherited in X-linked recessive and autosomal recessive patterns. X-linked variants occur in the CYBB gene, whereas autosomal recessive variants are found in the CYBA, NCF1, NCF2, NCF4, and CYBC1 genes.

RESULTS

This study analyzed data from 14 CGD patients across 12 families using functional, molecular, and genetic approaches. Among the patients, 11 (78.6%) had autosomal recessive inheritance, and 3 (21.4%) had X-linked recessive inheritance. The most common variants were in the NCF2 gene, followed by the CYBB, CYBA, and NCF1 variants. Consanguinity was observed in 72.7% of the autosomal recessive-CGD families. The most frequent clinical manifestations were lymphadenopathy (71.4%) and gastrointestinal symptoms (64.2%), followed by pulmonary symptoms, organomegaly, and abscesses (57%). The median age at diagnosis was 3 years, with a diagnostic delay ranging from 0 to 4 years, with an average of 17 months.

CONCLUSION

This study aims to increase awareness among Palestinian healthcare providers and encourage early consideration of CGD in patients with recurrent infections, even in late childhood.