Definition
- Primary humoral immunodeficiency with absent B cells and very low immunoglobulins
Aetiology
- X linked recessive mutation in Bruton tyrosine kinase (BTK)
- B cell maturation arrests at the pre B cell stage
Clinical Features
- Affects males
- Recurrent bacterial infections from about six months as maternal IgG wanes
- Sinopulmonary infection with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae
- Absent tonsils and lymph nodes
- Chronic enteroviral meningoencephalitis
- Oligoarthritis of knees, wrists, ankles and fingers
- Arthritis may be aseptic or septic
- Mycoplasma and Ureaplasma are recognised causes of septic arthritis
Investigations
- Low IgG, IgA and IgM
- B cells absent or near absent on flow cytometry
- BTK gene testing
- Joint aspirate culture often negative, so request Mycoplasma and Ureaplasma PCR
Differential Diagnosis
- Juvenile idiopathic arthritis
- Common variable immunodeficiency
- Septic arthritis in an immunocompetent child
Management
- Lifelong immunoglobulin replacement, IV or subcutaneous
- Aseptic arthritis often settles once immunoglobulin replacement is optimised
- Prolonged doxycycline or macrolide for Mycoplasma or Ureaplasma arthritis
- Surgical washout for septic joints as in other children
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.