X-linked Agammaglobulinemia (XLA)

X-linked agammaglobulinemia (XLA) is an X-linked syndrome that typically presents in childhood with recurrent sinopulmonary infections (otitis, sinusitis, pneumonia, etc.), low immunoglobulin levels and low or absent B cells. Patients may also have recurrent gastrointestinal infections (Giardia, Campylobacter, rotavirus, etc.), enteroviral meningoencephalitis, arthritis and inflammatory bowel disease.

Key Clinical Features

  • Recurrent sinopulmonary infections: Pneumonia, bronchitis, sinusitis, otitis media, etc.
  • Hypogammaglobulinemia: Markedly low IgG, IgM and IgA levels that become apparent after maternal antibody has diminished
  • Diminished lymphatic tissue: Small or absent tonsils, adenoids and lymph nodes
  • B lymphopenia: Low or absent B cell numbers

Molecular Defects Associated with XLA

  • Btk (Bruton's tyrosine kinase)
    • Inheritance: X-linked

Suggested Testing Approach

CIIT Xla Training Approach  

Specimen Requirements

  • Flow cytometry only or flow cytometry + gene sequencing: 7 cc whole blood in heparin sodium anticoagulant (green top tube) shipped overnight at ambient temperature. Please include 5-7 cc of whole blood from a normal individual in a separate tube as a control for flow cytometry studies in any shipped samples.
  • Gene sequencing only: 2-5 cc whole blood in heparin sodium or EDTA anticoagulant. Ship overnight at ambient temperature.
  • Alternative sources of DNA can be used as well (buccal swabs, CVS, etc.). Please contact the lab for questions or information.

Testing Methods

  • Flow cytometry: Platelets are evaluated by flow cytometry for intracellular Btk protein expression
  • Gene sequencing: All exons (-1 to 18) are evaluated by bidirectional sequencing from genomic DNA. Sequencing includes all exon/intron boundaries.

CPT Codes for Testing

  • Flow cytometry: 83907(1), 88184(1), 83912(1)
  • Btk gene sequencing: 83907(1), 83981(1), 83898(19), 83894(19), 83904(38), 83912(1)

Turnaround Times

  • Flow cytometry: Five business days from receipt of sample.
  • Gene sequencing: Btk - Four to six weeks from receipt of sample.

Testing Packet for X-linked Agammaglobulinemia

Sample Submission Form, Available Tests and Sample Requirements/Shipping Instructions (PDF)

See Also