Chronic granulomatous disease (CGD) describes an inherited genetic condition that affects a person’s immune system. It results in a type of immunodeficiency and causes people to be highly susceptible to certain bacterial and fungal infections.

CGD is a rare genetic condition that affects certain white blood cells and prevents the immune system from functioning correctly. It is a primary phagocytic immunodeficiency disorder, meaning it impacts immune cells known as phagocytes that eliminate certain bacteria and molds.

As such, people with CGD are more likely to experience frequent and severe infections. They may also experience chronic inflammation and clusters of white blood cells known as granulomas, hence the name of the condition.

In this article, we will discuss CGD, including its symptoms, causes, and treatment options.

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CGD refers to a rare genetic condition that affects the function of certain white blood cells. In particular, genetic variations impact the ability of immune cells, known as phagocytes, to produce components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This enzyme complex is responsible for eliminating pathogens such as bacteria and fungi.

As a result, people with CGD are prone to frequent infections, excessive inflammatory responses, and granuloma formation. CGD occurs due to changes in any one of five genes. It is usually an inherited condition, meaning a person acquires the gene variation from a biological parent. Evidence estimates that the condition occurs in 1 in 200,000–250,000 people worldwide.

It is a type of primary immunodeficiency disease (PIDD), which describes a genetic condition that impairs the immune system. Without a functional immune response, a person with a PIDD is susceptible to repeated infections, severe infections, and infections that are unusually hard to treat. While infections are problematic, many complications of CGD occur due to the chronic inflammation that a person experiences.

Typically, CGD occurs due to an alteration in one of five genes. These genes are responsible for producing subunits of NADPH oxidase, which plays a vital role in the immune system. Specifically, cells known as phagocytes use NADPH oxidase to produce a molecule called superoxide. This molecule helps kill foreign invaders and prevents them from multiplying and causing illness.

If none of these subunit proteins are unavailable, NADPH oxidase cannot assemble or function properly. Without it, phagocytes are unable to kill certain bacteria and fungi.

In addition to destroying pathogens, NADPH oxidase also plays a role in regulating the activity of immune cells called neutrophils. These cells play a role in adjusting the inflammatory response to help heal and reduce injuries. Therefore, without this enzyme complex, the body is susceptible to excessive inflammatory responses.

As CGD is a genetic condition, it is present from birth. Variations in any one of the following five genes may affect the effectiveness of NADPH oxidase:

The inheritance pattern of CGD is usually either X-linked recessive or autosomal recessive. This is why some people may refer to two types of CGD.

The most common type of CGD affects the CYBB gene and follows an X-linked recessive pattern. This means that the X chromosome carries the gene variation. Typically, females inherit one X chromosome from each biological parent. Conversely, males inherit an X chromosome from their biological mother and a Y chromosome from their biological father. This is why this type of CGD is more common in males, as they only inherit one X chromosome from their mother.

The other four genes follow an autosomal recessive pattern. This means that an individual must inherit two copies of the gene variation to display symptoms of CGD. As this type does not involve sex chromosomes, the risk is roughly the same for both males and females.

As CGD is a genetic condition, risk factors for passing it on include a parent either having the condition or being a carrier for a gene variation. Evidence suggests that infections occur most commonly with:

  • Staphylococcus aureus
  • Aspergillus species
  • Nocardia species
  • Serratia marcescens
  • Burkholderia cepacia

The characteristic features of CGD include:

  • an inability of phagocytes to kill certain types of bacteria and fungi
  • the presence of granulomas
  • chronic inflammation, even in the absence of infections

CGD may involve any organ or tissue of the body. However, infections are usually present in the:

  • skin
  • lungs
  • lymph nodes
  • liver
  • bones
  • occasionally the brain

A person will usually receive a diagnosis of CGD after a thorough clinical evaluation, medical history, and tests to evaluate their immune system and identify any gene variations. Typically, these tests may include:

  • neutrophil function tests to determine how well these immune cells are functioning
  • a dihydrorhodamine reduction test to measure oxidant production
  • a nitroblue tetrazolium slide test to also measure oxidant production

If the results of these tests indicate CGD, it is advisable for a person to undergo genetic testing. This screening will aim to confirm the presence of a gene alteration to determine the specific type of CGD.

Treatment options for CGD typically consist of continuous antibiotic therapy to help prevent bacterial and fungal infections. If a person with CGD acquires an infection, they generally require additional antibiotics and a longer time for the drugs to be effective. A doctor may also suggest corticosteroids and bone marrow transplants to help relieve symptoms.

A doctor may also recommend using Actimmune, also known as interferon gamma-1b. This protein may improve the activity of phagocytes, which could help reduce the number of severe infections. Ongoing research is also investigating gene therapy approaches to address the underlying genetic alterations that cause CGD. Some people may also consider genetic counseling when planning for pregnancy.

Additionally, it is advisable for an individual with CGD to try and prevent infections from occurring where possible. For example, this can include avoiding certain activities, such as:

  • swimming in fresh or salt water
  • using garden mulch in their yard
  • turning compost piles
  • repotting plants
  • cleaning cellars
  • riding on hay rides

Individuals living with CGD may have a slightly lower life expectancy due to recurring infections and chronic inflammation. However, a 2017 review highlights that the life expectancies of people with CGD have increased more than three-fold over the last few decades. This is likely due to the recognition of the condition and advances in treating and managing symptoms and complications.

CGD describes a rare genetic condition that impairs the immune system. It is a primary immunodeficiency disorder that affects the ability of phagocytes to fight off certain bacterial and fungal infections. In addition to a higher susceptibility to infections, a person may experience chronic inflammation and clusters of white blood cells known as granulomas.

Treatment options for CGD typically involve medications to help fight infections and reduce inflammation. Management of the condition includes trying to avoid exposure to organisms that, while safe for the general population, may cause infections in those with CGD.