Rare Nephrology News

Disease Profile

Chronic granulomatous disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

D71

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Granulomatous disease, chronic

Categories

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases;

Summary

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]

Symptoms

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]

    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.

    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

    Cause

    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).

    Diagnosis

    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.

    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.

      Treatment

      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]

      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]

      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.

      Organizations

      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

        Organizations Providing General Support

          Learn more

          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.
          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • MedlinePlus Genetics contains information on Chronic granulomatous disease. This website is maintained by the National Library of Medicine.
          • 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.

              References

              1. Nowicki RJ. Chronic Granulomatous Disease. Medscape Reference. 2018; https://emedicine.medscape.com/article/1116022-overview.
              2. Chronic Granulomatous Disease. NORD. 2018; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/682/viewAbstract.
              3. Chronic Granulomatous Disease. MedlinePlus Genetics. 2016; https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease/.
              4. Rosenzweig SD & Holland SM. Chronic granulomatous disease: Treatment and prognosis. UpToDate. 2018; https://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.

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