Years published: 1989, 1991, 1992, 1993, 1997, 1999, 2002, 2003, 2004, 2005, 2007, 2009, 2012, 2015, 2018, 2023
NORD gratefully acknowledges 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.
Chronic granulomatous disease (CGD) is a rare inherited primary immune deficiency disorder that affects certain white blood cells (neutrophils, monocytes, macrophages, eosinophils). The disorder is characterized by an inability to resist infections caused by certain types of bacterial and fungal species and a tendency to develop chronic inflammation. Life-threatening recurrent fungal and bacterial infections affecting the skin, lungs, liver and bones may occur. In addition, patients can develop swollen areas of inflamed tissues known as granulomas that can be widely distributed, as well as other inflammatory conditions, including those involving the gastrointestinal tract. 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 caused by changes (variants or mutations) in genes responsible for producing an important enzyme in white blood cells. Certain white blood cells use this enzyme to produce hydrogen peroxide that these cells need to kill certain bacteria and fungi and to properly regulate white blood cell responses to inflammation. These oxidants also regulate white blood cell pathways involved in the immune response and inflammation even in the absence of infection. Thus, patients with CGD have problems with both infections and increased inflammation.
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 gamma globulin 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 can show evidence of chronic infection. There may also be a persistent runny nose (rhinitis), inflammation of the skin (dermatitis) and an inflammation of the mucous membranes of the mouth (stomatitis). Gastrointestinal problems can also occur, including diarrhea, abdominal pain, colitis and perianal abscesses.
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 lung inflammation can develop in young adults with CGD.
Chronic granulomatous disease is a genetic disease. Changes (variants or 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 to kill certain bacteria and fungi and to properly regulate white blood cell responses to inflammation.
There is a form (X-linked recessive) of CGD that primarily affects males. The remaining cases of CGD are inherited in an autosomal recessive pattern, which can affect both males and females.
X-linked genetic disorders are conditions caused by a mutated gene on the X chromosome and mostly affect males. Females who have a mutated gene on one of their X chromosomes are carriers for that disorder. Carrier females usually do not have symptoms because females have two X chromosomes and only one carries the mutated gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a mutated 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 can reproduce, he will pass the mutated gene to all 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 children.
Recessive genetic disorders occur when an individual inherits a mutated gene from each parent. If an individual receives one normal gene and one mutated 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 mutated gene and have an affected child is 25% with each pregnancy. The risk of having 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 is 25%. The risk is the same for males and females.
Chronic granulomatous disease affects males more often than females. In North American and European studies, approximately, two-thirds of individuals have the X-linked recessive form of the disorder. 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 have chronic granulomatous disease.
A diagnosis of chronic granulomatous disease is made based upon a thorough clinical evaluation, a detailed patient history, and specialized procedures to measure oxidant production by white blood cells. In healthy individuals, the white blood cells produce a chemical oxidant that destroys bacteria. One blood test for diagnosis of CGD uses a molecule called dihydrorhodamine 123 (DHR) to determine whether white blood cells are making these oxidants normally. Oxidants cause the DHR to fluoresce, which is markedly reduced or absent in CGD white blood cells. This test can be performed on blood samples shipped to clinical laboratories certified to perform this test. Another blood test for CGD is called the nitroblue tetrazolium (NBT) slide test. In this test, NBT is mixed with the white blood cells, which are then activated to produce oxidants that react with NBT, turning it a deep blue color. If this reaction does not occur, then these important oxidants are not being produced by an individual’s white blood cells. If CGD is diagnosed based on defects in blood cell oxidant production, genetic testing is typically recommended to determine the specific type of CGD.
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 many affected individuals with CGD, with excellent outcomes especially when performed with matched donors at a younger age.
The orphan drug interferon gamma-1b (Actimmune) has been approved by the U.S.Food and Drug Administration (FDA) for the treatment of chronic granulomatous disease.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Gene therapy is being investigated in early-stage clinical trials as a possible treatment for CGD. This involves a type of bone marrow transplant using the patient’s own marrow cells. Information on this and other current clinical trials for CGD 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. Some trials in other countries are also posted on this 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: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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
Dinauer M. Chronic Granulomatous Disease. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:386-87.
Gennery AR. Progress in treating chronic granulomatous disease. Br J Haematol. 2021;192(2):251-264.
Marciano BE, Zerbe CS, Falcone EL, et al. X-linked carriers of chronic granulomatous disease: illness, lyonization and stability. J Allergy Clin Immunol. 2018:41:365-371
Dinauer MC. Primary immune deficiencies with defects in neutrophil function. Hematology Am Soc Hematol Educ Program. 2016:43-50.
Thomsen IP, Smith MA, Holland SM, Creech CB. A comprehensive approach to the management of children and adults with chronic granulomatous disease. J Allergy Clin Immunol Pract. 2016;4(6):1082-1088.
Kuhns DB, Alvord WG, Heller T, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600-10.
Gallin JL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003; 348:2416-22.
Johnson RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001; 8:17-22.
Segal BH, Leto TL, Gallin JI, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000; 79:170-200.
Leiding JW, Holland SM. Chronic Granulomatous Disease. 2012 Aug 9 [Updated 2022 Apr 21]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK99496/ Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome b-Positive, Type II. Entry No: 233710. Last Edited 07/20/2020. Available at: http://omim.org/entry/233710 Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Granulomatous Disease, Chronic, X-Linked; CGD. No: 306400. Last Edited 02/22/2022. Available at: http://omim.org/entry/306400 Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Atypical mycobacteriosis, familial, X-linked 2; AMCBX2. Entry No: 300645. Last Edited 10/28/2015.Available at: http://omim.org/entry/300645 Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome b-Positive, Type I. Entry No: 233700. Last Edited 03/01/2022. Available at: http://omim.org/entry/233700 Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome b-Negative. Type IV Entry No: 233690. Last Edited 07/07/202. Available at: http://omim.org/entry/233690 Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome b-Positive, Type III. No: 613960. Last Edited 07/07/2020. Available at: http://omim.org/entry/613960 Accessed August 9, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Granulomatous Disease, Chronic, Autosomal Recessive, Type V, Entry No. 618334. Last edited 07/07/2020. Available at https://omim.org/entry/618334.Accessed August 9, 2023.
Chronic granulomatous disease. MedlinePlus. 12/4/2022. http://www.nlm.nih.gov/medlineplus/ency/article/001239.htm Accessed August 9, 2023.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/
Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/
This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/