Key Clinical and Laboratory Features

  • Common clinical features: Recurrent sinopulmonary infections (pneumonia, bronchitis, sinusitis and otitis media), most often caused by Streptococcus pneumoniae and Hemophilus influenza.
  • Other clinical features: Recurrent gastrointestinal infections (giardia, campylobacter, rotavirus, etc.), bacterial skin infections (Pseudomonas, Helicobacter pylori), sepsis, arthritis, inflammatory bowel disease, enteroviral meningoencephalitis and dermatomyositis
  • Physical exam: Minimal lymphatic tissue (small or absent tonsils, adenoids and lymph nodes)
  • Common laboratory features: Hypogammaglobulinemia (markedly low IgG that becomes apparent after the loss of maternal antibodies as well as low or absent IgM and IgA), low or absent specific antibody titers, B-cell lymphopenia

Testing Approach

  Test Comments
Gene BTK Gene Sequencing The gold standard for confirming a diagnosis of BTK deficiency in a patient with symptoms.
Protein BTK Protein by Flow Since XLA patients generally have few B cells, BTK protein expression needs to be evaluated in either platelets or monocytes. Approximately 75–80% of patients with BTK mutations have low or absent BTK expression in platelets and monocytes and can be identified using this test. There are patients with missense mutations in BTK that express a normal amount of non-functional BTK protein.
Function N/A There are currently no available clinical tests to evaluate BTK protein function.
Other
  • Lymphocyte subset analysis: B-cell lymphopenia is common in patients.
  • Quantitative immunoglobulin levels: IgG universally low. IgA and IgM may be low as well.
  • Specific antibody titers: universally low.