Chronic granulomatous disease

What causes chronic granulomatous disease?

Chronic granulomatous disease is caused by changes (mutations) in one of five genes ( CYBA , CYBB , NCF1 , NCF2 , or NCF4 ). Each gene encodes a different part (subunit) of an enzyme called NADPH oxidase, which is essential to the immune system. One function of this enzyme is to help make toxic substances that are used to kill bacteria and fungi that invade the body before they can cause infection. It may also play a role in regulating the activity of immune cells that help manage the inflammatory response. Mutations in these genes lead to reduced levels of NADPH oxidase and in severe cases, no enzyme is produced. As a result, the immune system can not function properly, leaving the body vulnerable to frequent infections and chronic inflammation.

For background information on how the body naturally responds to invading bacteria, visit the link about the immune system offered by the National Institute of Allergy and Infectious Diseases (NIAID).

Last updated on 05-01-20

How is chronic granulomatous disease diagnosed?

A diagnosis of chronic granulomatous disease is often suspected based on the presence of characteristic signs and symptoms. Specialized blood tests, such as the nitroblue tetrazolium test and/or flow cytometry with dihydrorhodamine, can then be ordered to confirm the diagnosis. Both of these tests can be used to determine whether or not the immune cells are making toxic substances that the body uses to fight infections.

The diagnosis of CGD is established with identification of the mutation(s) in one of five genes:

  • CYBA, NCF1, NCF2 , and NCF4 (the genes related to autosomal recessive chronic granulomatous disease)
  • CYBB is the gene related to the X-linked chronic granulomatous disease.

Last updated on 05-01-20

How is chronic granulomatous disease inherited?

When chronic granulomatous disease is caused by changes (mutations) in the CYBA, NCF1 , NCF2 , or NCF4 genes, it is inherited in an autosomal recessive manner. This means that a person must have a change in both copies of the disease-causing gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. The CYBB gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one mutated copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two mutated copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Rarely, females with one mutated copy of the CYBB gene have mild symptoms of chronic granulomatous disease, such as an increased frequency of bacterial or fungal infections.

Last updated on 05-01-20

Are people with chronic granulomatous disease eligible for disability?

Eligibility for disability depends not on diagnosis, but degree of condition involvement and impairment. For further information regarding your eligibility, you may find it helpful to speak with a social worker at your local hospital. In addition, you may benefit from visiting, which provides quick and easy access to comprehensive information about disability programs, services, laws and benefits.

Last updated on 05-01-20

What is the long-term outlook for people with chronic granulomatous disease?

The long-term outlook (prognosis) for people with chronic granulomatous disease varies depending on the severity of their condition. Frequent infections and episodes of inflammation can reduce the life expectancy of people with the condition. However, recent advances in therapy have drastically improved the survival and quality of life. In fact, the average person with chronic granulomatous disease now survives at least 40 years, due in large part to routine use of prophylactic therapies.

Last updated on 05-01-20

How might chronic granulomatous disease be treated?

Chronic granulomatous disease is usually managed with antibiotic and antifungal medications to treat and prevent infection. Corticosteriods may be used to shrink granulomas (areas of inflamed tissue). Treatment may also include a medication called Actimmune (also known as interferon gamma-1b). Actimmune is a man-made version of a substance normally produced by the body's immune cells and has been shown to decrease the frequency of severe infections in people with chronic granulomatous disease.

Early diagnosis of infection is very important, so people with chronic granulomatous disease are generally followed closely by a medical professional. The frequency of follow-up will depend on the severity of the condition.

A bone marrow transplant (allogeneic hematopoietic stem cell transplantation or HSCT) may be used to treat and possibly cure chronic granulomatous disease, however HSCT has serious risks including the possibility of severe disability or death. Although the risks associated with HSCT are decreasing due to medical advances, HSCT is usually only considered for those severely affected by chronic granulomatous disease.

Medical researchers believe gene therapy also holds great promise as a future cure, but more clinical studies are needed to determine if gene therapy will be both safe and effective for those with chronic granulomatous disease. As medical researchers better understand chronic granulomatous disease, new treatments that help control the immune system (immunomodulatory agents) may also become available.

Last updated on 05-01-20

Where To Start

CGD Society

The CGD Society has an information page on Chronic granulomatous disease. Please click the link to access this resource.

Last updated on 04-27-20

Name: Immune Deficiency Foundation 110 West Road, Suite 300
Towson, MD, 21204, United States
Toll Free: 1-800-296-4433 Fax : +1-410-321-9165 Email: Url:
Name: Chronic Granulomatous Disease Association, Inc. c/o Mary Hurley 2616 Monterey Road
San Marino, CA, 91108, United States
Phone: 626-441-4118 Url:
Name: CGD Society PO Box 454
Dartford, DA1 9PE, United Kingdom
Phone: 0800 987 8988 Email: Url:
Name: Primary Immune Deficiency UK PID UK PO Box 6970
Basingstoke, RG24 4XL, United Kingdom
Toll Free: 0800 987 8986 Email: Url:

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