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 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 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, 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 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 at least 4-5 abnormal genes that are present in one copy. 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 due to two copies of the same abnormal gene.
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.
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:
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.
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
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/.
For information about clinical trials conducted in Europe, contact:
As of Spring, 2015, 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 bone marrow stem cell transplant procedures in CGD patients.
2. Studying and developing gene therapy for treating CGD.
3. New approaches for treating liver abscesses in CGD patients.
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
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