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Chronic Granulomatous Disease

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

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NORD is very grateful to Mary C. Dinauer, MD, PhD, Department of Pediatrics and Department of Pathology & Immunology, St. Louis Children's Hospital, Washington University School of Medicine, for assistance in the preparation of this report.

Synonyms of Chronic Granulomatous Disease

Disorder Subdivisions

General Discussion

Chronic granulomatous disease (CGD) is a rare inherited primary immune deficiency disorder that affects certain white blood corpuscles (neutrophils, monocytes, macrophages, eosinophils). The disorder is characterized by an inability to resist repeated infectious diseases and a tendency to develop chronic inflammation. Life-threatening recurrent fungal and bacterial infections affecting the skin, lungs, and bones may occur along with swollen areas of inflamed tissues known as granulomas that can be widely distributed. Symptoms usually begin in infancy or childhood. Individuals with mild forms of the disorder may not develop symptoms until the teens or adulthood. Chronic granulomatous disease is a genetic disorder and is caused by inherited defects in an important enzyme in white blood cells that manufactures oxidants for microbial killing.


Chronic granulomatous disease is characterized by a susceptibility to repeated bacterial and fungal infections. CGD can also be associated with the development of granulomatous lesions of the skin, lungs, bones, and lymph nodes formed by collections of inflammatory white blood cells. Excess gammaglobulin in the blood (hypergammaglobulinemia), low levels of circulating red blood cells (anemia), an increase in white blood cells (leukocytosis) can occur as a result of repeated infections or chronic inflammation. Evidence of chronic infections may be seen in the liver, gastrointestinal tract, brain and eyes.

There is usually a history of repeated infections, including inflammation of the lymph glands (suppurative lymphadenitis), skin infections, and pneumonia. Blood studies often show evidence of chronic infection. There may also be a persistent runny nose (rhinitis), inflammation of the skin (dermatitis), diarrhea, perianal abscesses, and an inflammation of the mucous membranes of the mouth (stomatitis).

Infection of the bones (osteomyelitis), brain abscesses, obstruction of the genitourinary tract and/or gastrointestinal tract due to the formation of granulomatous tissue, and delayed growth are also symptomatic of chronic granulomatous disease. Abnormal enlargement of the liver and spleen (hepatosplenomegaly) may also occur.


Chronic granulomatous disease is a genetic disease. In CGD, mutations in any one of five different genes can cause a defect in an enzyme called phagocyte NADPH oxidase. Certain white blood cells use this enzyme to produce hydrogen peroxide, which these cells need in order to kill certain bacteria and fungi.

Genetic diseases are determined by two genes, one received from the father and one from the mother. There is a genetic form (X-linked recessive) of CGD that primarily affects males. The remaining cases of CGD are inherited as autosomal recessive traits, which can affect both males and females.

X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have a defective gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the defective gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a defective gene he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the defective gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Chronic granulomatous disease affects males more often than females. Approximately, two-thirds of individuals have the X-linked recessive form of the disorder. Because it is a genetic disease, CGD is present at birth. Symptoms from CGD usually first occur during infancy or childhood, but sometimes may be delayed until the early teens. In a few cases, the first symptoms have been known to occur in adulthood.

It is estimated that about four to five in every million people worldwide has chronic granulomatous disease.

Related Disorders

Symptoms of the following disorders can be similar to those of chronic granulomatous disease. Comparisons may be useful for a differential diagnosis:

Wegener's granulomatosis is an uncommon collagen vascular disorder affecting the blood vessels. It begins as a localized inflammation of the upper and lower respiratory tract mucous membranes, and usually progresses into generalized inflammation of the blood vessels (vasculitis) and kidney (glomerulonephritis). Initial symptoms usually appear as a severe cold progressing to sinusitis, ulcerations of the mucous membranes in the nose with secondary bacterial infection, middle ear infection (otitis media), cough, expectoration of blood (hemoptysis) and pleuritis. The nasal mucous membrane appears red with a raised granular appearance. There may also be fever, loss of appetite and generalized discomfort. (For more information on this disorder, choose "Wegener" as your search term in the Rare Disease Database.)

Sarcoidosis is a multisystem disorder that most often affects individuals between 20 and 40 years of age. It is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) consisting of certain granular white blood cells (modified macrophages or epithelioid cells) in certain organs of the body. The granulomas that are formed are thought to alter the normal structure of and, potentially, the normal functions of, the affected organ(s), causing symptoms associated with the particular body system(s) in question. In individuals with sarcoidosis, such granuloma formation most commonly affects the lungs. However, in many cases, the upper respiratory system, lymph nodes, skin, and/or eyes may be involved. In addition, in some cases, other organs may be affected, including the liver, bone marrow, spleen, musculoskeletal system, heart, salivary glands, and/or nervous system (i.e., central or peripheral nervous system). The range and severity of symptoms associated with sarcoidosis vary greatly, depending upon the specific organ(s) involved and the degree of such involvement. In some cases, the symptoms of sarcoidosis may begin suddenly (acute), sometimes severely, and subside in a relatively short period of time (self limited). Acute sarcoidosis is often characterized by fatigue, fever, generalized muscle aches, difficulty breathing (dyspnea), joint pain, swollen glands, skin eruptions, eye irregularities, and/or other symptoms. In the subacute form, affected individuals may experience no symptoms (asymptomatic), even with organ involvement. In the chronic form of sarcoidosis, symptoms may appear slowly and subtly, and may persist or recur over a long time span. Symptoms associated with other organ involvement may follow. The exact cause of sarcoidosis is not known. (For more information on this disorder, choose "Sarcoidosis" as your search term in the Rare Disease Database.)

Churg-Strauss syndrome is a rare disorder that may affect multiple organ systems, particularly the lungs. The disorder is characterized by the formation and accumulation of an unusually large number of antibodies, abnormal clustering of certain white blood cells (eosinophilia), inflammation of blood vessels (vasculitis), and the development of inflammatory nodular lesions (granulomatosis). Many individuals with Churg-Strauss syndrome have a history of allergy. In addition, asthma and other associated lung (pulmonary) abnormalities (i.e., pulmonary infiltrates) often precede the development of the generalized (systemic) symptoms and findings seen in Churg-Strauss syndrome by one or more years. Asthma, a chronic respiratory disorder, is characterized by inflammation and narrowing of the lungs' airways, causing difficulties breathing (dyspnea), coughing, and/or other symptoms and findings. Nonspecific findings associated with Churg-Strauss syndrome typically include flu-like symptoms, such as fever, a general feeling of weakness and fatigue (malaise), loss of appetite (anorexia), weight loss, and muscle pain (myalgia). Additional symptoms and findings may be variable, depending upon the specific organ systems involved. Although the exact cause of Churg-Strauss syndrome is unknown, many researchers indicate that abnormal immunologic and autoimmune factors play an important role. (For more information on this disorder, choose "Churg-Strauss" as your search term in the Rare Disease Database.)

Polyarteritis nodosa is characterized by an inflammation of the small and medium sized arteries causing narrowing of the vessels. This may result in a lack of blood supply to tissues, possible formation of blood clots (thrombosis), and weakening, ballooning (aneurysm) or possible rupture of the vessel walls. Joint, muscle, abdominal and testicular pain may occur. The patient may also have fever, weight loss and high blood pressure (hypertension). The kidney is the organ most involved. The lungs are rarely affected. Skin rash may be present and gastrointestinal symptoms such as abdominal pain, vomiting of blood (hematemesis) and tender abdomen may be present. (For more information on this disorder, choose "Polyarteritis Nodosa" as your search term in the Rare Disease Database.)

Standard Therapies

A diagnosis of chronic granulomatous disease is made based upon a thorough clinical evaluation, a detailed patient history, and a specialized procedure called nitroblue tetrazolium (NBT) slide test. During this procedure, a blood sample is taken to obtain white blood cells. NBT is then mixed with the white blood cells. In healthy individuals, the white blood cells produce a chemical oxidant that destroys bacteria. This chemical also reacts with NBT turning it a deep blue color. If this reaction does not occur, then this important chemical is not being produced by an individual's white blood cells. Another similar test for diagnosis of CGD uses a molecule called dihydrorhodamine 123 (DHR) to determine whether or not white blood cells are making oxidants normally.

Treatment of chronic granulomatous disease consists of continuous antibiotic therapy to help prevent infections, such as trimethoprim and sulfamethoxazole to protect against bacterial infections, and itraconazole for anti-fungal protection. Infections usually require additional antibiotics. Corticosteroid drugs are also of benefit for treating granulomatous complications. Bone marrow transplants have proven to be successful in some affected individuals with CGD.

The orphan drug, Actimmune (interferon gamma-1b), has been approved by the Food and Drug Administration (FDA) for the treatment of chronic granulomatous disease. For information on this drug, contact the manufacturer:

InterMune, Inc.
3280 Bayshore Blvd.
Brisband, CA 94005
Tel.: (415) 466-2200
Fax: (415) 466-2300

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Clinical trials related to CGD can also be found by searching the web site at http://clinicaltrials.gov/.

As of Autumn, 2012, the NIH listed multiple clinical trials to investigate possible treatments for chronic granulomatous disease (CGD), and include as follows:

1. Several different studies to determine the efficacy and safety of stem cell transplant procedures in CGD patients.

2. Studying and developing gene therapy for treating CGD.

3. Studying the response of white blood cells from CGD patients to interferon-gamma treatment.

Contact for additional information about chronic granulomatous disease:

Mary C. Dinauer, MD, PhD
Fred M. Saigh Distinguished Chair of Pediatric Research
Professor of Pediatrics and of Pathology & Immunology
Washington University School of Medicine
St. Louis Children’s Hospital
660 S. Euclid Ave.
Campus Box 8208
St. Louis, MO 63110
Office: 314-286-0542
Fax: 314-286-2893
Website: http://peds.wustl.edu

Chronic Granulomatous Disease Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Chronic granulomatous disease. MedlinePlus. http://www.nlm.nih.gov/medlineplus/ency/article/001239.htm. Updated September 15, 2010. Accessed September 10, 2012.

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Report last updated: 2012/09/12 00:00:00 GMT+0