Chronic granulomatous disease - Genetics Home Reference
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Chronic granulomatous disease
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Reviewed August 2012
What is chronic granulomatous disease?
Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and fungi. Individuals with chronic granulomatous disease have recurrent bacterial and fungal infections. People with this condition often have areas of inflammation (granulomas) in various tissues that can be damaging to those tissues. The features of chronic granulomatous disease usually first appear in childhood, although some individuals do not show symptoms until later in life.
People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease are susceptible to a condition called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes.
Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that can lead to stomach pain, diarrhea, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth and throat. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys, bladder, and genitalia. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system.
Rarely, people with chronic granulomatous disease develop autoimmune disorders such as myasthenia gravis, which causes muscle weakness, and juvenile rheumatoid arthritis, which causes joint pain and swelling. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs.
Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood.
People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease are susceptible to a condition called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes.
Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that can lead to stomach pain, diarrhea, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth and throat. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys, bladder, and genitalia. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system.
Rarely, people with chronic granulomatous disease develop autoimmune disorders such as myasthenia gravis, which causes muscle weakness, and juvenile rheumatoid arthritis, which causes joint pain and swelling. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs.
Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood.
How common is chronic granulomatous disease?
Chronic granulomatous disease is estimated to occur in 1 in 200,000 to 250,000 people worldwide.
What genes are related to chronic granulomatous disease?
Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. There are five types of this condition that are distinguished by the gene that is involved. The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Specifically, NADPH oxidase is primarily active in immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. Within phagocytes, NADPH oxidase is involved in the production of a toxic molecule called superoxide. Superoxide is used to generate other toxic substances, which play a role in killing foreign invaders and preventing them from reproducing in the body and causing illness. NADPH oxidase is also thought to regulate the activity of immune cells called neutrophils. These cells play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body.
Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. Mutations in the genes that cause chronic granulomatous disease that prevent the production of any functional protein are designated "0". For example, mutations in the CYBB gene that lead to no functional beta subunit are designated CYBB0. Mutations that lead to a reduction of the amount of protein produced are designated "-", for example, CYBB-.
Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to kill foreign invaders and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation.
Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown.
Read more about the CYBA, CYBB, NCF1, NCF2, and NCF4 genes.
Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. Mutations in the genes that cause chronic granulomatous disease that prevent the production of any functional protein are designated "0". For example, mutations in the CYBB gene that lead to no functional beta subunit are designated CYBB0. Mutations that lead to a reduction of the amount of protein produced are designated "-", for example, CYBB-.
Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to kill foreign invaders and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation.
Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown.
Read more about the CYBA, CYBB, NCF1, NCF2, and NCF4 genes.
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