SNP Shot: Genomic Insights

Chronic granulomatous disease (CGD) is an immune system disorder, classified as an immunodeficiency. This means the immune system's ability to defend the body against bacteria and fungi is compromised. Individuals with CGD are prone to recurring infections caused by these pathogens. They may also develop granulomas, which are areas of inflammation, in various tissues, potentially leading to tissue damage. Although symptoms of CGD usually appear in childhood, some individuals may not experience them until later in life.

Individuals with CGD typically experience at least one serious bacterial or fungal infection every 3 to 4 years. Lung infections are the most common, with pneumonia being a frequent occurrence. A specific type of fungal pneumonia called mulch pneumonitis can develop after exposure to decaying organic matter like mulch, hay, or dead leaves, resulting in fever and shortness of breath. This is because these materials contain numerous fungi, which can cause lung infections in individuals with CGD. Other common sites for infections include the skin, liver, and lymph nodes.

Inflammation, in the form of granulomas, can affect various parts of the body in individuals with CGD. The gastrointestinal and genitourinary tracts are commonly affected. Inflammation of the intestinal wall can cause inflammatory bowel disease, with varying degrees of severity, leading to symptoms like stomach pain, diarrhea, bloody stool, nausea, and vomiting. Other common sites of inflammation include the stomach, colon, rectum, mouth, throat, and skin. Granulomas in the gastrointestinal tract can also lead to tissue breakdown and abscesses (pus-filled pockets). Stomach inflammation can cause gastric outlet obstruction, preventing food from passing into the intestines and impairing digestion. This can lead to vomiting after eating and weight loss. In the genitourinary tract, inflammation can affect the kidneys and bladder. Furthermore, inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), both involved in immune cell production, can further weaken the immune system.

In rare cases, individuals with CGD may develop autoimmune disorders, where the immune system mistakenly attacks the body's own tissues and organs.

The repeated cycle of infections and inflammation associated with CGD can shorten life expectancy. However, with appropriate treatment, most individuals with CGD can live into mid- to late adulthood.

Inheritance:

When CGD is caused by mutations in the CYBB gene, it follows an X-linked recessive inheritance pattern. The CYBB gene resides on the X chromosome, one of the sex chromosomes. Males, possessing only one X chromosome, will develop CGD if they inherit one altered copy of the CYBB gene. Females, with two X chromosomes, require mutations in both copies of the gene to develop the disorder. As it's less likely for females to have two altered copies, X-linked recessive disorders are more common in males. A key feature of X-linked inheritance is that fathers cannot pass these traits to their sons. In rare instances, females with one altered copy of the CYBB gene may experience mild CGD symptoms, such as more frequent bacterial or fungal infections. When CGD is caused by mutations in the CYBA, NCF1, NCF2, or NCF4 genes, it follows an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must carry mutations for the condition to develop. Individuals with autosomal recessive conditions inherit one copy of the mutated gene from each parent, who typically do not exhibit signs or symptoms of the condition themselves. Autosomal recessive conditions affect males and females equally.