Chronic granulomatous disease (CGD): Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management

Document Type: Review


1 Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran

2 Alborz University of Medical Sciences, Karaj, Iran.

3 Alborz University of Medical Sciences, Karaj, Iran

4 Department of Sports and Exercise Medicine, Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, Tehran, Iran Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

5 Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran



Chronic granulomatous disease (CGD) is a relatively rare inborn error of immune system caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex which leads to impaired production of reactive oxygen species (ROS) and ineffective phagocyte function. Genetic defects of any of proteinaceous components of NADPH oxidase complex results in CGD. The most common type of CGD (65-70%) is caused by X-linked mutations in the CYBB gene encoding gp91phox, followed by autosomal recessive mutations in the NCF1, NCF2, CYBA and NCF4 genes encoding p47phox, p67phox, p22phox, and p40phox, respectively. Dihydrorhodamine (DHR) 123 oxidation and nitroblue tetrazolium (NBT) tests are both used for the diagnosis of CGD that should be confirmed by genetic testing. CGD patients generally present with recurrent infections caused by uncommon pathogens like aspergillus, staphylococcus aureus, burkholderia cepacia, serratia marcescens, Aspergillus species and nocardia. They manifest with deep seated abscess formation, genitourinary and gastrointestinal granuloma development, autoimmunity and malignancy. Apart from comprehensive treatment of acute infections, management of CGD is based on reducing bacterial and fungal infections in addition to minimizing the inflammatory symptoms. Antibiotics, anti-fungal and IFN-γ are used for prophylaxis. Allogeneic hematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD. Gene therapy is considered an alternative, novel therapeutic approach in near future.