Congenital agammaglobulinemia is inherited as an X-linked recessive trait, with the defect lying in the impaired differentiation process from pre-B cells to B cells. This disease occurs only in males and is also known as Bruton's disease.

bubble_chart Clinical Manifestations

After 4 to 6 months of birth, the protective effect of maternal IgG disappears, and severe purulent bacterial infections begin to recur frequently, especially upper and lower respiratory tract infections. Common conditions include purulent bronchitis, pneumonia, otitis media, and may also involve meningitis, osteomyelitis, and suppurative arthritis. However, there is no particular susceptibility to toxins or fungi. The child's lymph nodes are underdeveloped, and the tonsils are small or absent. Despite recurrent infections, the lymph nodes and spleen do not enlarge.

[Auxiliary Examination]

1. The total serum immunoglobulin is less than 250 mg/dl, IgG is less than 200 mg/dl, and IgA, IgM, IgD, and IgE are barely detectable.

2. Circulating B cells with surface Ig or Ia-like antigens are significantly reduced, which differs from common variable immunodeficiency.

3. Isohemagglutinins are absent or present at very low titers.

4. The antibody response to vaccination is extremely low or absent.

5. The peripheral blood lymphocyte count is normal, with an increased percentage of T cells and very few B cells (<0.5%) or none. The T/B cell ratio is elevated.

6. Cellular immune function is normal.

Lymph node and tonsil biopsies show a lack of germinal centers and plasma cells (while the bone marrow contains a normal number of pre-B cells).

bubble_chart Treatment Measures

The principle is to use replacement therapy to supplement the antibodies that the patient cannot produce. The method involves periodic intramuscular injections of human serum immunoglobulin, with a dose of 0.7 ml/kg of gamma globulin per month. Normal serum IgG is approximately 12.0 g/L. Although this regimen can only maintain the patient's serum IgG at a level of 2.0 g/L, it has significant therapeutic effects. Long-term repeated injections may cause local scar formation at the injection site, and occasionally fever, rash, urticaria, asthma, and shock-like reactions such as decreased blood pressure, which should be promptly treated as anaphylactic shock. For patients who do not respond to intramuscular gamma globulin or cannot tolerate the pain, continuous intravenous infusion of plasma at 10 ml/kg can be administered to increase serum immunoglobulin levels. Additionally, intravenous immunoglobulin at 600 ml/kg per month may be given; administering antihistamines or hydrocortisone before infusion can significantly reduce the side effects of globulin[7]. For various infections, antibiotic treatment is recommended. The combination of trimethoprim and sulfamethoxazole is effective for chronic sinus and lung infections caused by IgA deficiency.

1. Transient hypogammaglobulinemia of infancy: (1) Serum IgG is very low, while IgA and IgM are normal. (2) Peripheral blood B-cell count is normal. (3) Lymph node biopsy shows plasma cell-like lymphocytes despite the absence of mature plasma cells. (4) The ability to synthesize immunoglobulins usually recovers within 18 months.

2. Normal infants aged 5-9 months: (1) Although serum IgG is low, it remains above 350 mg/dl. (2) IgM and IgA can be detected in the serum.