Chronic granulomatous disease (CGD) [8 genes]

Chronic granulomatous disease (CGD) is a disorder of neutrophils, where impaired NADPH oxidase activity is caused by a defect in one of the five protein subunits of the NADPH oxidase complex, resulting in failure to kill certain bacteria and fungi. The proteins of the NADPH oxidase complex are encoded by genes CYBB, CYBA, NCF1, NCF2, and NCF4. Genetic counseling and specific prognosis are possible after the disease-causing mutation detection.

• 1/250,000 individuals

• Differential diagnosis and genetic counseling
• Hematopoietic stem cell transplantation (HSCT)
• Gene therapy
• Prophylaxis with antibacterials and/or antifungals

The identification of a disease-causing genetic defect in one of the panel’s genes allows for a precise molecular diagnosis of the disease and the appropriate genetic counseling based on the inheritance pattern associated with the genetic finding. Prevention of primary manifestations in CGD is important and includes antibiotic/antifungal prophylaxis, immunomodulatory therapy, and HSCT transplantation.

CGD should be suspected when a patient presents, especially caused by severe or chronic bacterial infections:

• Childhood growth restriction
• Pneumonia
• Lymphadenitis
• Osteomyelitis
• Abscesses or cellulitis
• Granuloma formation, especially in the genitourinary and gastrointestinal tract
• Colitis
• Abnormal wound healing due to excess granulation

CGD-associated infections involve a restrictive spectrum of pathogens, so pathogen isolation is useful to direct suspicion of the disease. Biochemical tests of direct measurement of superoxide production in neutrophils also allow the establishment of CGD diagnosis.

The precise diagnosis of CGD is established when a pathogenic genetic defect is identified in one of the genes that make up the CGD panel.