Bruton's Tyrosine Kinase
Utility:1) Diagnostic screen for X-linked agammaglobulinemia (XLA).
2) Detection of carrier status in female relative of XLA.
3) Evaluation of hypogammaglobulinemia in male patients.
Specimen: 4 - 10 mL peripheral blood in sodium heparin (green top).
CPT codes: 86359, 86360, 86355, 86357, 88184, 88185 x 5, 88188.
Clinical indication/general description
X-linked agammaglobulinemia (XLA), also known as Bruton's agammaglobulinemia, is characterized by a marked reduction or absence of peripheral blood B cells and profound hypogammaglobulinemia of all isotypes (IgG, IgA, IgM and IgE). Patients with XLA present in early childhood with recurrent infections, in particular with encapsulated bacteria, as well as chronic enteroviral infections. XLA is caused by mutations in the Bruton's Tyrosine Kinase (BTK) gene, which is essential for the development of B cells. Some mutations in BTK result in a milder clinical and laboratory phenotype and are therefore described as leaky.
XLA presents with severe reduction or absence of B cells (CD19+). Therefore, BTK protein expression is determined in CD14+ monocytes since these cells also express BTK. In XLA, monocytes express either no or very low amounts of BTK protein. Women who carry the mutated allele express normal numbers of B cells that produce normal levels of BTK due to nonrandom X inactivation. However, only 50 percent of monocytes express the BTK protein and this observation can be used to determine carrier status of relatives of affected children.