Chronic Granulomatous Disease (CGD) is a rare genetic disorder that affects the immune system, specifically the ability of certain white blood cells to effectively kill bacteria and fungi. This condition is caused by mutations in genes that provide instructions for making proteins involved in the immune system's defense mechanism. The most common genes affected in CGD are CYBB, NCF1, NCF2, and NCF4.
1. Genetic Mutations: The primary cause of CGD is genetic mutations in the genes responsible for producing proteins involved in the formation of reactive oxygen species (ROS) within white blood cells. These ROS play a crucial role in destroying harmful bacteria and fungi. Mutations in the CYBB gene, which codes for the gp91phox protein, are the most common cause of CGD, accounting for approximately 65% of cases. Mutations in other genes, such as NCF1, NCF2, and NCF4, can also lead to CGD.
2. Inherited Disorder: CGD is an inherited disorder, meaning it is passed down from parents to their children. It follows an X-linked recessive pattern, which means that the mutated gene is located on the X chromosome. As a result, CGD primarily affects males, while females are typically carriers of the mutated gene.
3. Impaired Phagocyte Function: CGD primarily affects phagocytes, a type of white blood cell responsible for engulfing and destroying harmful microorganisms. In individuals with CGD, phagocytes are unable to produce sufficient amounts of ROS, which are essential for killing bacteria and fungi. As a result, these individuals have impaired immune responses and are more susceptible to recurrent and severe infections.
4. Increased Susceptibility to Infections: Due to the impaired function of phagocytes, individuals with CGD are highly susceptible to infections caused by certain bacteria and fungi. Common infections associated with CGD include pneumonia, skin abscesses, lymphadenitis, and liver or gastrointestinal infections. These infections can be severe, recurrent, and difficult to treat.
5. Diagnosis: CGD is typically diagnosed through a combination of clinical evaluation, laboratory tests, and genetic testing. The presence of recurrent or severe infections, along with abnormal laboratory findings indicating impaired phagocyte function, can raise suspicion for CGD. Genetic testing can confirm the diagnosis by identifying specific mutations in the genes associated with CGD.
6. Treatment: While there is no cure for CGD, various treatment options are available to manage the condition and prevent infections. Antibiotics are commonly prescribed to treat and prevent infections. Additionally, prophylactic antifungal medications may be recommended. In severe cases, a bone marrow or stem cell transplant may be considered as a potential curative option.
In conclusion, Chronic Granulomatous Disease is primarily caused by genetic mutations in genes involved in the immune system's defense mechanism. These mutations impair the function of phagocytes, leading to an increased susceptibility to severe and recurrent infections. CGD is an inherited disorder that primarily affects males. While there is no cure, treatment options are available to manage the condition and prevent infections.