Unlocking the Mysteries of Chronic Granulomatous Disease: A Guide to Diagnosis and Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Chronic granulomatous disease (CGD) is a rare genetic disorder that affects the immune system. This condition is characterized by the inability of immune cells called phagocytes to effectively eliminate certain bacteria and fungi. As a result, individuals with CGD are prone to recurrent and severe infections. One type of CGD, autosomal due to deficiency of CYBA, is caused by mutations in the CYBA gene, which leads to the dysfunction of a protein called p22-phox. In this article, we will explore the complexities of this disease, the process of diagnosis, and the role of genetic testing in managing the condition.

Understanding Chronic Granulomatous Disease, Autosomal, Due to Deficiency of CYBA

The immune system is our body’s primary defense against infections. In CGD, a specific component of the immune system, the phagocytes, are unable to function properly. Phagocytes are responsible for engulfing and destroying harmful bacteria and fungi. The dysfunction of phagocytes in CGD is due to a deficiency of a protein called p22-phox, which is encoded by the CYBA gene. This deficiency impairs the ability of phagocytes to produce reactive oxygen species, which are essential for killing pathogens.

Individuals with CGD often experience recurrent and severe infections, especially in the skin, lungs, and lymph nodes. These infections can lead to the formation of granulomas, which are clusters of immune cells that form in response to chronic inflammation. Granulomas can cause damage to the affected tissues and organs, leading to further complications.

Diagnosing Chronic Granulomatous Disease

Diagnosing CGD can be challenging, as its symptoms can be similar to those of other conditions. A thorough medical history and physical examination are essential for identifying the signs and symptoms of CGD. The diagnosis is typically confirmed through laboratory tests that assess the function of phagocytes. These tests may include:

• Nitroblue tetrazolium (NBT) test: This test measures the ability of phagocytes to produce reactive oxygen species. A decreased production of these molecules is indicative of CGD.
• Dihydrorhodamine 123 (DHR) assay: This test also evaluates the production of reactive oxygen species by phagocytes. It is considered to be more sensitive and specific than the NBT test.
• Flow cytometry: This technique is used to measure the expression of specific proteins on the surface of immune cells, which can help to identify the specific type of CGD.

Once a diagnosis of CGD is confirmed, genetic testing can be performed to determine the specific gene mutation responsible for the disease. This information can be crucial for guiding treatment and management strategies, as well as for providing genetic counseling to affected families.

The Role of Genetic Testing in Chronic Granulomatous Disease

Identifying the Specific Mutation

Genetic testing for CGD involves analyzing the DNA sequence of the genes associated with the disease, such as the CYBA gene. By identifying the specific mutation responsible for the deficiency of p22-phox, healthcare providers can gain a better understanding of the severity and progression of the disease. This information can also be used to inform treatment decisions and to predict the likelihood of complications.

Carrier Testing and Prenatal Diagnosis

For families with a history of CGD, genetic testing can be used to identify carriers of the disease-causing mutation. Carrier testing is particularly important for couples who are planning to have children, as it can help to determine the risk of passing the mutation to their offspring. In some cases, prenatal diagnosis may also be possible, allowing for early detection and management of the disease in affected fetuses.

Guiding Treatment and Management Strategies

Genetic testing can provide valuable information for guiding the treatment and management of CGD. For example, individuals with certain gene mutations may be more likely to respond to specific therapies, such as interferon-gamma or gene therapy. Additionally, knowledge of the specific mutation can help healthcare providers to monitor for potential complications and to tailor treatment plans accordingly.

In conclusion, understanding the complexities of chronic granulomatous disease, autosomal, due to deficiency of CYBA is crucial for accurate diagnosis and effective management of the condition. Genetic testing plays a key role in identifying the specific mutation responsible for the disease, guiding treatment decisions, and providing valuable information for affected families. As our understanding of CGD continues to grow, so too will our ability to improve the lives of those living with this challenging condition.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)