Chronic Granulomatous Disease - CGD

Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder characterized by severe, recurring infections with formation of granulomas. Phagocytic cells ingest but cannot digest bacteria or fungi due to a malfunction of the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase system.


Indications for Testing

Severe and recurrent bacterial and fungal infections, presence of granulomas, colitis, pneumonias, osteomyelitis, lymphadenitis

Laboratory Testing

  • Nonspecific testing to rule out other disorders
    • Serum quantitative immunoglobulins – rule out disorders associated with immunoglobulin deficiency
    • Complement activity enzyme immunoassay – rule out complement deficiency
    • CBC with differential – rule out other causes of chronic infection (eg, neutropenic disorders)
    • Leukocyte adhesion deficiency panel – rule out leukocyte adhesion deficiency
  • Specific testing
    • Neutrophil oxidative burst assay (dihydrorhodamine [DHR]) via flow cytometry
      • Preferred screening test
      • Disease is indicated by absence or significant alteration of activity
    • Other, less reliable tests
      • Measurement of superoxide production, ferricytochrome C reduction, nitroblue tetrazolium test
  • Genetic testing
    • X-linked chronic granulomatous disease (CGD) – CYBB gene
    • Autosomal recessive CGD – CYBA, NCF1, NCF2, NCF4 genes

Differential Diagnosis



  • Incidence – 1/250,000 births
  • X-linked CGD
    • CYBB – 60-70% of cases
  • Autosomal recessive CGD
    • NCF1 – 25% of cases
    • CYBA – <5% of cases
    • NCF2 – <5% of cases
    • NCF4 – very rare
  • Age – dependent on type of CGD
    • Classic X-linked in males – typically <3 years
    • Carrier females of X-linked – usually >3 years
    • Females with skewed X-chromosome inactivation – similar to males
  • Sex – M>F by 85%


  • X-linked form – 60-70% of cases
    • Involves CYBB gene mutations in the 13 exons encoding the 91-kD heavy chain of cytochrome b558
      • Typically earlier onset and more severe disease than autosomal recessive CGD
  • Autosomal recessive forms
    • NCF1 – encodes p47phox
      • GT deletion in exon 2 (c.75_76delGT) accounts for ~85% of causative variants in NCF1 (Vázquez, 2001)
    • CYBA – encodes p22phox
    • NCF2 – encodes p67phox
    • NCF4 – encodes p40phox


  • Function of phagocytes (neutrophils and macrophages)
    • First line of defense against bacterial and fungal infections
    • Migrate to the site of infection – phagocytosis occurs, which generates microbicidal reactive oxygen products
    • Neutrophils and macrophages are ingested by the phagosome
    • Other nonoxidative factors are added that assist in killing pathogenic microorganisms
  • CGD – abnormalities of neutrophils and macrophages
    • Gene mutations cause defective microbicidal oxidant production secondary to a defect in the neutrophil respiratory burst
    • Results in decreased production of superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorite ions within neutrophils and macrophages
      • Defective production causes susceptibility to infections from organisms that may be nonpathogenic in an immunocompetent individual
      • Most common infections – bacterial (eg, catalase-positive microorganisms) and fungal organisms

Clinical Presentation

  • Signs and symptoms usually appear very early in childhood for X-linked male cases
    • May not present until later in life, especially with mild cases or autosomal recessive/variant forms of X-linked CGD
  • Ophthalmic – chorioretinitis
  • ​Oral – periodontitis, gingivitis, stomatitis, aphthous ulcerations
  • Gastrointestinal – nausea, diarrhea, vomiting, colitis/enteritis with inflammatory bowel disease (IBD)-like manifestations (blood in stool, granulomas in gastrointestinal tract), splenomegaly, hepatitis
  • Genitourinary – urethral/ureteral strictures, bladder granulomas, urinary tract infections
  • Pulmonary – pneumonia, obliterative bronchiolitis, bronchiectasis 
  • Skin and musculoskeletal – lymphadenitis, skin and visceral abscesses, osteomyelitis
  • Infections
    • Chronic obstructive granulomas form at sites of infection
    • Characterized by bacterial and fungal infections, with most common agents including
      • Staphylococcus aureus
      • Burkholderia cepacia
      • Serratia marcescens
      • Nocardia spp
      • Aspergillus spp
  • Concomitant autoimmune disorders

ARUP Laboratory Tests

Primary Tests

Aid in screening for chronic granulomatous disease (CGD)

Results are not intended to be used as the sole means for clinical diagnosis or patient management decisions

Specimen must remain ambient and be tested within 48 hours of collection

Related Tests

Initial test in workup of immunoglobulin disorders

Order in conjunction with serum protein electrophoresis and immunofixation to rule out plasma cell dyscrasia in adults and older children (>15 years) with suspected hypogammaglobulinemia

Panel includes IgA, IgG, and IgM

Initial screening for suspected deficiency in the classical complement pathway

Aids in the diagnosis of type 1 and 2 leukocyte adhesion deficiency

Panel measures CD11a, CD11b, CD15, and CD18 on neutrophils

Useful when a pathogenic familial variant identifiable by sequencing is known

Consultation with a genetics counselor is advised


Additional Resources

Medical Experts



Harry R. Hill, MD
Professor of Pathology (Clinical), Pediatrics, and Medicine, University of Utah
Medical Director, Cellular and Innate Immunology, ARUP Laboratories