SNP Shot: Genomic Insights

X-linked agammaglobulinemia (XLA) is an immune system disorder primarily affecting males. Classified as a primary immunodeficiency, or an inborn error of immunity, XLA results from a malfunctioning immune system. Individuals with XLA have a significant deficiency in B cells, specialized white blood cells crucial for fighting infections. B cells develop into cells that produce antibodies (immunoglobulins), proteins that target and neutralize foreign invaders. Due to this antibody deficiency, individuals with XLA are highly vulnerable to infections.

Infants with XLA typically remain healthy for the first one to two months due to protection from maternal antibodies received before birth. However, once these antibodies diminish, affected children begin experiencing recurrent infections. These infections often persist or recur despite antibiotic treatment, and recovery may be prolonged.

Common bacterial infections in individuals with XLA include pneumonia, bronchitis, otitis (ear infections), conjunctivitis (pink eye), and sinusitis (sinus infections). Chronic diarrhea-causing infections are also frequently observed. Repeated infections can lead to organ damage. Antibody replacement therapies can prevent infections and improve the well-being of individuals with XLA.

Inheritance:

XLA follows an X-linked recessive inheritance pattern. The gene responsible for XLA is located on the X chromosome, a sex chromosome. Males, possessing only one X chromosome, develop XLA if they inherit a single altered copy of the gene. Females, with two X chromosomes, require two altered copies to develop the condition. Consequently, XLA and similar X-linked recessive disorders are far more prevalent in males than females. Mothers of affected individuals may carry one altered copy of the BTK gene. These carriers typically do not exhibit XLA's immune system abnormalities but can transmit the altered gene to their children. Fathers cannot pass X-linked traits to their sons but can pass them to their daughters. Approximately half of individuals with XLA have no known family history of the condition. In these instances, the affected individual carries a new, spontaneous variant in the BTK gene, not inherited from either parent.