X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by genetic defects in the
Bruton tyrosine kinase (Btk) gene. XLA is characterized as an antibody deficiency by recurrent
bacterial infections, the absence of peripheral B cells, and profound reductions in all
immunoglobulin isotypes. This study aims to report the clinical and genetic features of five Iranian patients with XLA. Five male cases with recurrent
bacterial infection entered this study based on clinical evaluation and Immunological screening tests. The levels of
T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) were also measured in dried blood spot (DBS) samples. Sanger sequencing was applied to PCR products of
DNA samples of the patients for genetic studies. All patients were from unrelated families with a mean age of 6.7 years (2.5-11) at the time of diagnosis with 4.8 mean years of delay in diagnosis. The most frequent clinical manifestations were recurrent
respiratory infections and
arthritis. In these patients, five previously reported mutations were found including four mutations (p.Q496X, p.Q497X, p.R520X, and p.R641H) in the
Kinase domain besides one mutation (p.L37P) in the
pleckstrin homology (PH) domain. Evaluations of KREC and TREC level in patients' DBS showed low-to-undetectable copies of KREC (0-2 copies/3.2mm DBS) with normal copies of TREC. As patients with XLA have complete
immunoglobulin defects and develop severe and
recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. The study results may provide valuable information for the diagnosis, genetic counseling and prenatal diagnosis for the patients and their family members and emphasize performing KREC as an early diagnostic test in patients with XLA.