What are other Names for this Condition? (Also known as/Synonyms)

• Chronic Dysphagocytosis
• Chronic Granulomatous Disease of Childhood
• Progressive Septic Granulomatosis

What is Chronic Granulomatous Disease? (Definition/Background Information)

• Chronic Granulomatous Disease (CGD) is a genetic disorder that can occur as either an X-linked recessive disorder or as an autosomal recessive disorder. It mostly affects males worldwide, and causes a severe weakening of the body’s immune system
• It is caused by a mutation in any one of five critical genes that are responsible for an immune response against infectious organisms. These critical genes assist in the formation of oxidase enzyme that aids the white blood cells (WBCs) in killing infectious pathogens 
• The signs and symptoms of Chronic Granulomatous Disease are typically severe and result from bacterial and fungal infections. It is typically diagnosed following an evaluation of one’s medical history and specific blood tests for genetic mutations
• Skin damage, swollen lymph nodes and recurrent pneumonia can be complications that result from infections associated with Chronic Granulomatous Disease. These may be severe and even fatal without adequate management
• The treatment for Chronic Granulomatous Disease usually revolves around continuous antibiotic therapy and anti-fungal medication in order to prevent acquiring infections. Due to the genetic nature of CGD, there are no methods available to prevent it, other than genetic counseling to raise awareness of the condition
• The prognosis is good with suitable treatment in a majority of cases. Individuals diagnosed with Chronic Granulomatous Disease may lead normal lives on consistently taking necessary precautions to avoid infections

Who gets Chronic Granulomatous Disease? (Age and Sex Distribution)

• Chronic Granulomatous Disease (CGD) is rare and occurs in about 1 in 200,000-250,000 people worldwide
• Since it is a genetic disease, it is present in the affected individuals at birth; the signs and symptoms usually begin to show during infancy and childhood. In some cases, the symptoms do not begin to show until early teenage
• Chronic Granulomatous Disease is an X-linked recessive disorder in about 50% of the cases, and so it affects males more than females. Autosomal recessive CGD cases are known to affect both males and females equally
• Chronic Granulomatous Disease can affect people of any ethnic or geographical group worldwide showing no preference to any specific race or ethnicity

What are the Risk Factors for Chronic Granulomatous Disease? (Predisposing Factors)

• A positive family history of Chronic Granulomatous Disease (CGD) is a risk factor for the condition
• It is also reported that a family history of frequent infections may be an indicator that there may be an increased risk for CGD
• Presently, there are no other risk factors established for CGD

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Chronic Granulomatous Disease? (Etiology)

• Chronic Granulomatous Disease is caused by a mutation in any of the five genes which results in the body’s inability to make an oxidase enzyme found in the white blood cells (WBCs)
• This NADPH oxidase enzyme makes hydrogen peroxide that gives white blood cells the natural ability to kill foreign pathogens such as bacteria and fungi
• Chronic Granulomatous Disease can be inherited in either an X-linked recessive or autosomal recessive manner

X-linked recessive: X-linked recessive: X-linked recessive conditions are traits or disorders that occur when two copies of an abnormal gene are inherited on a sex chromosome (X or Y chromosome). All X-linked recessive traits are fully evident in males because they have only one copy of the X chromosome. This means that there is no normal gene present to mask the effects of the mutant copy. All males who are affected will pass the mutated gene onto their female offspring, because they must inherit one copy of the X chromosome from each parent. This means that they will be unaffected carriers. Females are rarely affected by X-linked recessive disorders because they have two copies of the X chromosome. In the rare case that they inherit two mutated copies of the gene, they will inherit the condition.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Chronic Granulomatous Disease?

The signs and symptoms of Chronic Granulomatous Disease are typically the result of the body’s inability to fight off bacterial and fungal infections.

The signs and symptoms may include:

• Blisters or sores on the face
• High fever
• Body aches
• Growths or boils filled with pus
• Eczema: Skin disorder that causes itchy rashes on the body
• Swollen lymph nodes
• Repeated infections and pneumonia
• Gastrointestinal issues including diarrhea and stomach pain
• Formation of granulomatous lesions on the skin, lungs, bones, and lymph nodes formed by inflamed white blood cells

When the blood is affected in Chronic Granulomatous Disease, the following may be noted:

• Excess gammaglobulin (a protein that makes up antibodies) in blood
• Low red blood cell count (anemia)
• Increased amount of white blood cells (leukocytosis) in blood

How is Chronic Granulomatous Disease Diagnosed?

Chronic Granulomatous Disease (CGD) is diagnosed by a healthcare professional following a physical examination and a careful examination of the individual’s medical history. Typically, the condition may be suspected after a child begins to show signs of recurrent infections.

• The main test used to detect CGD includes taking a blood sample and extracting the white blood cells to see if they produce the oxidant hydrogen peroxide
• Blood cultures are taken if blood infection (septicemia) is suspected
• Bone scans and chest X-rays may be taken to identify infections
• Testing for specific genetic mutations associated with CGD may be undertaken

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Chronic Granulomatous Disease?

The possible complications of Chronic Granulomatous Disease include:

• Skin damage due to repeated infection
• Swollen lymph nodes that may either stay swollen or keep becoming swollen. Lymph nodes may form abscesses that can require surgery to drain them 
• Chronic nose infections
• Lung infection (pneumonia) that is recurrent and difficult to cure, leading to lung damage
• Bone damage from infections due to chronic and acute osteomyelitis 
• The infection can spread to blood, causing blood poisoning (septicemia) that can damage vital organs in the body
• Overall decreased quality of life

Severe infections, if left untreated can be fatal.

How can Chronic Granulomatous Disease be Treated?

The optimum treatment for Chronic Granulomatous Disease includes taking measures to prevent the bacterial or fungal infections.

• Continuous antibiotic therapy helps prevent bacterial infections
• Antifungal medications may be needed to prevent fungal infections
• Corticosteroids can be used to treat granulomatous lesions that can affect tissue function. The steroids should be carefully taken under guidance of a qualified healthcare provider
• Severe abscess formations may require surgery to drain them 
• Avoiding situations that may increase one’s risk of getting respiratory infections such as gardening activities, turning compost piles, using mulch, repotting plants, dealing with hay, cleaning cellars, etc.
• In some cases, bone marrow transplants have proven successful in helping some individuals with Chronic Granulomatous Disease

Close follow-up and regular monitor of the condition is necessary and recommended.

How can Chronic Granulomatous Disease be Prevented?

Currently, there are no specific methods or guidelines to prevent Chronic Granulomatous Disease since it is a genetic condition.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Seeking medical attention at the first signs of an infection is strongly advised.

What is the Prognosis for Chronic Granulomatous Disease? (Outcomes/Resolutions)

• With prompt, adequate and continuous management of Chronic Granulomatous Disease (CGD), the affected individuals can have better outcomes. An individual is often able to live a normal life with certain limitations
• Without antibiotic or antifungal treatments for infection, the prognosis for those with CGD is unfavorable to poor, with individuals having greatly shortened lifespans

Additional and Relevant Useful Information for Chronic Granulomatous Disease:

The likelihood for two parents who carry the gene for autosomal recessive version of Chronic Granulomatous Disease to have a child with the disease is:

• 25% to have a child affected by Chronic Granulomatous Disease with each pregnancy
• 50% to have a child who is a carrier of the abnormal gene but not necessarily be affected by the disease, just like the parents, with each pregnancy
• 25% to have child that is completely normal for the gene causing Chronic Granulomatous Disease