X-linked agammaglobulinemia is a disorder of primary immunodeficiency that induces poor production of B lymphocytes. The clinical presentation starts in late infancy and early childhood as maternal antibodies provide adequate protection during the first several months of life. Various forms of recurrent bacterial infections (and enteroviral infections) are the main manifestation of X-linked agammaglobulinemia, which may be life-threatening in the absence of an early therapy. The diagnosis rests on clinical suspicion, laboratory workup, and genetic studies that confirm Bruton tyrosine kinase (Btk) mutations.
X-linked agammaglobulinemia is a form of primary immunodeficiency caused by mutations in the Btk gene, which plays a key role in the maturation and proliferation of B cells     . Given the X-linked recessive mode of inheritance, the condition appears almost exclusively in males and the prevalence rate is established to around 1 in 10,000 in the general population  . The clinical presentation usually starts in the first few years of life, but only after the maternal IgG antibodies cease to protect the infant   . At some point, first signs and symptoms appear and the mean onset is established to be between 2-3 years of age  . The main complaint is in the form of recurrent and persistent infections   . Individuals are particularly susceptible to encapsulated organisms such as Haemophilus influenzae, Pseudomonas spp., and Streptococcus pneumoniae  . Although the immunological response to viral infections remains largely intact, enteroviral infections do occur and can even be life-threatening . Lower respiratory tract infections are the most common types, whereas otitis media, conjunctivitis, gastrointestinal infections, sinusitis, and cutaneous infections are also frequently reported   . Recent advances in treatment have led to markedly improved patient outcomes. Almost 60% of patients are diagnosed when severe, life-threatening infections develop .
Suspicion toward a primary immunodeficiency must be raised in the presence of recurrent infections in early life, particularly because of the life-threatening risk that is established in this patient population. Moreover, a misdiagnosis until adulthood has been reported. The early recognition can significantly improve the quality of life     . For this reason, physicians should take a detailed patient history, during which the onset of symptoms and their progression should be revealed, whereas a family history must also be obtained . After a physical examination, a detailed laboratory investigation needs to be employed. All classes of serum immunoglobulins are usually decreased in patients suffering from X-linked agammaglobulinemia  . In addition, the number of B lymphocytes in the blood is markedly reduced  . To confirm the diagnosis, however, molecular genetic studies must be performed. Btk protein testing that detects either mutation (missense, splice, and nonsense mutations have all been recognized) or reduced expression is considered to be a definitive method for establishing X-linked agammaglobulinemia as the underlying cause    .