X-linked agammaglobulinemia in a 10-year-old boy with a novel non-invariant splice-site mutation in Btk gene

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk). Most XLA patients have severely reduced or absent peripheral blood B cells and serum immunoglobulins, since the expression or function of Btk, critical for the maturation of B cell lineages at pro-B and pre-B cell stages, is deficient. Early and accurate diagnosis of XLA is important, since the affected patients suffer from severe and recurrent infections unless they receive intravenous immunoglobulin (IVIG) replacement therapy. However, the diagnosis of XLA is not always easy because some patients have detectable (∼ 2%) B cells in the peripheral blood and have significant levels of serum immunoglobulins. In this study, we report on a patient who was diagnosed with XLA at the age of 10 years. The diagnosis was delayed due to near-normal levels of serum immunoglobulins, although he presented with severe and recurrent bacterial infections since the age of 1 year. He was demonstrated to have a novel non-invariant splice-site mutation in intron 10 (IVS10 − 11C → A) of the Btk gene, which was not detected by the standard PCR-based mutation analysis. This mutation resulted in no detectable Btk expression. This case suggests that patients suffering from severe or recurrent bacterial infection should be suspected to have XLA even though they may have significant levels of serum immunoglobulins. Furthermore, significant levels of serum immunoglobulins in XLA patients do not necessarily mean less severe phenotype.