Problems begin after 6 months of life when maternal immunoglobulins (Ig) levels drop.
About
- X-linked Agammaglobulinaemia (XLA), also known as Bruton's disease, was first described by Dr. Bruton in 1952.
- The molecular defect responsible for XLA has been identified as a mutation in the BTK gene (Bruton's tyrosine kinase).
- BTK is a kinase involved in signal transduction pathways crucial for the maturation of B cells.
Aide-memoire
- Boys, Bruton, B cells, and BTK - an easy way to remember the key features of XLA, which primarily affects male children due to its X-linked inheritance.
Aetiology
- The BTK gene defect causes a failure in the maturation of B cells, leading to severely reduced circulating B cells and plasma cells.
- This results in the inability to produce sufficient antibodies (immunoglobulins), leaving patients vulnerable to infections.
Clinical Features
- Problems typically begin after 6 months of age when maternal Ig levels decrease.
- Primarily presents in boys with recurrent and severe bacterial infections.
- Patients often have small lymph nodes and absent tonsils due to the lack of mature B cells.
- Common infections include bacterial meningitis, joint infections, otitis media, and pneumonia.
- Pathogens include Mycoplasma, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.
Investigations
- Full Blood Count (FBC): Shows an absence of circulating B cells.
- Immunoglobulin levels are profoundly low, with decreased levels of IgG, IgM, and IgA.
- ↓ IgG ↓ IgM ↓ IgA with absent B cells.
Management
- The mainstay of treatment is immunoglobulin replacement therapy (Ig therapy), which successfully reduces the frequency and severity of infections.
- Avoid live vaccines, as these can pose a risk to immunocompromised patients.
Long-term Complications
- Patients may develop juvenile rheumatoid arthritis or aseptic polyarthritis.
- Other complications include dermatomyositis and an increased risk of colorectal neoplasms.