National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare, inherited immunodeficiency that affects certain white blood cells. People with this condition have immune systems that do not function properly, leaving the body vulnerable to chronic inflammation and frequent bacterial and fungal infections. The features of this condition usually develop in infancy or early childhood; however, milder forms may be diagnosed in the teen years or even in adulthood.[1][2] It is caused by changes (mutations) in any one of five different genes and is usually inherited in an autosomal recessive or X-linked recessive manner.[3] Treatment consists of continuous therapy with antibiotic and antifungal medications to treat and prevent infections.[1][4] The only cure for the disease is an allogeneic hematopoietic stem cell transplantation (HSCT).[5] 
Last updated: 11/18/2016
In people with chronic granulomatous disease, the immune system does not work properly, which leaves the body vulnerable to certain types of bacteria and fungi. The features of the condition usually develop in infancy or early childhood; however, milder forms may be diagnosed in the teen years or even in adulthood. The signs and symptoms vary but may include:[1][2][3]
Last updated: 11/18/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of neutrophils 0001874
Chronic pulmonary obstruction 0006510
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity
[ more ] 		0000992
Fever 0001945
Hepatomegaly
Enlarged liver
0002240
Hypermelanotic macule
Hyperpigmented spots
0001034
Malabsorption
Intestinal malabsorption
0002024
Mediastinal lymphadenopathy
Swollen lymph nodes in center of chest
0100721
Otitis media
Middle ear infection
0000388
Pyloric stenosis 0002021
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Sinusitis
Sinus inflammation
0000246
Tracheoesophageal fistula 0002575
5%-29% of people have these symptoms
Eczema 0000964
Gingivitis
Inflamed gums
Red and swollen gums
[ more ] 		0000230
Inflammatory abnormality of the eye 0100533
Liver abscess 0100523
Meningitis 0001287
Sepsis
Infection in blood stream
0100806
Skin ulcer
Open skin sore
0200042
Splenomegaly
Increased spleen size
0001744
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Last updated: 7/1/2020
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.[3]

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: 11/18/2016
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.[5][3] 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.[3]
Last updated: 11/18/2016
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.[1][2]

The diagnosis of CGD is established with identification of the mutation(s) in one of five genes:[12468]
  • 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: 11/18/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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.[1][2][4][5][6] 

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.[1][2][4]

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.[1][2][4][5]

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.[4][5] As medical researchers better understand chronic granulomatous disease, new treatments that help control the immune system (immunomodulatory agents) may also become available.[6]
Last updated: 12/19/2016

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

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.[1][4] 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.[4]
Last updated: 11/18/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes cystic fibrosis, Crohn disease, hyper-IgE syndrome, allergic bronchopulmonary aspergillosis, glutathione synthetase deficiency, and secondary hemophagocytic lymphohistiocytosis (see these terms). Myeloperoxidase deficiency (see this term) must also be excluded, as it gives a false positive for the DHR assay test.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Chronic granulomatous disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Chronic granulomatous disease. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Chronic granulomatous disease:
    European Society for Immunodeficiencies (ESID) Registry
    United States Immunodeficiency Network (USIDENT) Registry
     
  • The Primary Immune Deficiency Treatment Consortium (PIDTC) is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with severe combined immunodeficiency, Wiskott-Aldrich syndrome, and chronic granulomatous disease through research. The Primary Immune Deficiency Treatment Consortium (PIDTC) has a registry for patients who wish to be contacted about clinical research opportunities.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • Good Days provides help to patients with life-altering conditions. Assistance includes help with the cost of medications and travel.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The CGD Society has an information page on Chronic granulomatous disease. Please click the link to access this resource.
  • Genetics Home Reference (GHR) contains information on Chronic granulomatous disease. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers. 
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Merck Manual for health care professionals provides information on Chronic granulomatous disease.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Chronic granulomatous disease in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Chronic granulomatous disease. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • The information I have read said that most infections occur in younger people. I have not had any major problems until now at 56 years of age. Should I be under a doctors care regularly? Am I a candidate for disability? See answer


  1. Nowicki RJ. Chronic Granulomatous Disease. Medscape Reference. 2018; http://emedicine.medscape.com/article/1116022-overview.
  2. Chronic Granulomatous Disease. NORD. 2018; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/682/viewAbstract.
  3. Chronic Granulomatous Disease. Genetics Home Reference. 2016; http://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease.
  4. Rosenzweig SD & Holland SM. Chronic granulomatous disease: Treatment and prognosis. UpToDate. 2018; http://www.uptodate.com/contents/chronic-granulomatous-disease-treatment-and-prognosis.
  5. Leiding JW & Holland SM. Chronic Granulomatous Disease. GeneReviews. February 11, 2016; https://www.ncbi.nlm.nih.gov/books/NBK99496/.
  6. Vignesh P, Rawat A & Singh S. An Update on the Use of Immunomodulators in Primary Immunodeficiencies. Clin Rev Allergy Immunol.. Nov 21 2016; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/27873163.