Chronic Granulomatous Disease




CGD is a rare disease. There are about 20 people born with CGD each year in the United States.

People with CGD have an immune system that doesn’t work properly. A healthy immune system usually prevents infections from becoming serious. An immune system with CGD can typically stop viral infections like a cold or flu, but can’t stop serious infections started by certain bacteria and fungi. Since CGD is a chronic condition, it means that a person will have the disease for all of his or her life.

CGD isn’t something you can catch. It’s a genetic condition, which means you’re born with it. It’s passed down to a child from 1 or both parents who can be “carriers.” A carrier doesn’t have the disease, but his or her children can end up with it. Carriers of CGD have 1 normal copy of the gene and 1 copy of the gene that doesn’t work right. There are 2 types of CGD: X-linked and autosomal recessive.

X-linked CGD

The most common form of CGD is X-linked. It’s passed down from the mother because she carries a faulty X chromosome. This means she is a carrier of CGD. Usually only males get X-linked CGD. A male born to a carrier mother has a 50% chance of having CGD.


CGD is usually diagnosed before a child is 5 years old. Some males and females with milder forms of CGD may not show signs until they are a teen or an adult. Common signs and symptoms to look for include:

  • Lymph nodes infection or granuloma
  • Liver abscesses
  • Colitis
  • Bones Infection
  • Pneumonia
  • Stomach granuloma
  • Urinary tract granuloma

Other symptoms include diarrhea, weight loss, or abdominal pain due to inflammation in the intestines, pain or difficulty eating or going to the bathroom, fever, cough, joint pain, and being tired all of the time.

When determining whether you have CGD, it’s important to discuss your entire medical history with your doctor. CGD can be misdiagnosed as inflammatory bowel disease (IBD) because the symptoms are similar.


CGD is caused by mutations in any one of the 6 genes encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits or a critical stabilizer. A mutation in the CYBB gene (Xp21.1) is seen in 65% of cases in North America and Western Europe. The other 35% of cases are due to mutations in the CYBA (16q24), NCF1 (7q11.23), NCF2 (1q25), NCF4 (22q13.1) and CYBC1(17q25.3) genes. A deficiency in the NADPH oxidase enzyme complex leads to decreased production of reactive oxygen species (used by phagocytes to kill bacteria and fungi). The X-linked form of CGD typically presents with infection or IBD earlier than the NCF1-related form. To date, the NCF4-related form has only been associated with IBD but no severe infections.


Diagnostic methods

Diagnosis is suspected on clinical findings and confirmed by laboratory tests. Nitroblue tetrazolium (NBT) or dihydrorhodamine (DHR) oxidation assays measure the neutrophil superoxide production by the NADPH oxidase complex, which is absent or greatly reduced. Molecular genetic testing can be used to confirm the diagnosis and identify the specific subunit affected, but is not necessary unless gene therapy or allogeneic transplantation are anticipated. Immunoblot analysis can confirm the absence of the specific NADPH oxidase complex subunit involved.

Differential diagnosis

Differential diagnosis includes cystic fibrosis, Crohn disease, hyper-IgE syndrome, allergic bronchopulmonary aspergillosis, glutathione synthetase deficiency, and secondary hemophagocytic lymphohistiocytosis. Myeloperoxidase deficiency must also be excluded, as it gives a false positive for the DHR assay test.

Antenatal diagnosis

Prenatal diagnosis is possible in families with a disease-causing mutation.


The prognosis of CGD is improving with advancements in treatment. Patients can prevent infection with good skin hygiene, antifungals, and antibiotics. Autosomal recessive forms of CGD have a better prognosis compared to X-linked CGD. On average, CGD patients survive at least 40 years, especially with long-term prophylactic antimicrobials. Often a severe fungal or bacterial infection can be fatal. Aspergillus is the most common fungal respiratory infection and is the most common cause of death in CGD. Mortality and morbidity will continue to decrease as advances are made in prophylactic methods, HSCT, and other immunomodulatory therapy


Antibacterial and antifungal prophylaxis is essential in preventing the infections seen in CGD. Lifelong daily doses of trimethoprim-sulfamethoxazole (antibacterial) and itraconazole (anti-fungal) are recommended. Interferon-gamma, 3 times weekly, is also recommended. Hematopoietic stem cell transplantation may be curative and is increasingly used. Gene therapy has been successful in a few cases and is expanding. In those with severe infections, granulocyte transfusions are sometimes used.