Agammaglobulinemia

Agammaglobulinemia is a rare genetic disorder characterized by the absence or severe reduction of gamma globulins in the blood, which are a major component of antibodies. This condition results in an individual's increased susceptibility to infectious diseases, particularly bacterial infections, due to an impaired immune system.

Etiology

Agammaglobulinemia can be either congenital or acquired. The most common form of congenital agammaglobulinemia is X-linked agammaglobulinemia (XLA), which is caused by mutations in the BTK gene. This gene is crucial for B cell development, and mutations here lead to a block in B cell maturation, resulting in a lack of B cell production and consequently, very low levels of serum immunoglobulins.

Acquired forms of agammaglobulinemia, although rare, can occur due to a variety of causes including certain medications, chronic lymphocytic leukemia, and other conditions that affect immune system function.

Clinical Presentation

Patients with agammaglobulinemia typically present in early childhood, often after the age of six months when maternal antibodies (transferred through the placenta) begin to wane. Common symptoms include recurrent bacterial infections such as otitis media (middle ear infections), pneumonia, sinusitis, and skin infections. Without proper treatment, these infections can be severe and may lead to chronic lung damage.

Diagnosis

Diagnosis of agammaglobulinemia involves a series of tests, including:

• Measurement of serum immunoglobulin levels, which are typically markedly reduced or absent.
• Flow cytometry to analyze B cell numbers, which are usually very low or absent in individuals with XLA.
• Genetic testing to identify mutations in the BTK gene or other genes associated with the condition.

Treatment

The primary treatment for agammaglobulinemia is immunoglobulin replacement therapy, which involves regular infusions of antibodies to help prevent infections. This treatment does not cure the underlying defect but helps to manage the symptoms and improve the quality of life.

Patients also require prompt antibiotic treatment for any infections and may benefit from preventive measures such as vaccinations with killed or inactivated organisms. However, live vaccines are contraindicated due to the risk of infection.

Prognosis

With regular treatment, the prognosis for individuals with agammaglobulinemia has improved significantly. Most can lead relatively normal lives, although they continue to be at higher risk for certain infections and may experience complications related to chronic lung disease.

See Also

• Primary immunodeficiency
• B cell
• Immunoglobulin therapy