X-linked Agammaglobulinemia (XLA)
The diagnosis is B - X-linked agammaglobulinemia (XLA), based on the constellation of recurrent sinopulmonary infections, recurrent giardiasis, absent lymph nodes, and family history of sepsis death in a male relative. 1, 2
Key Diagnostic Features That Confirm XLA
The absence of palpable lymph nodes is pathognomonic for XLA and immediately distinguishes it from other immunodeficiencies. 1, 2 Patients with XLA characteristically lack lymphoid tissue due to absent or severely reduced B cells, presenting with small or absent tonsils and non-palpable lymph nodes. 1, 2
The clinical pattern strongly supports XLA:
Recurrent sinopulmonary infections (6 episodes) are the hallmark of XLA, occurring in 88% of patients, with upper respiratory tract involvement in 75% and lower respiratory tract in 65%. 1, 3
Recurrent giardiasis (>4 episodes) occurs in 35% of XLA patients, often presenting with chronic diarrhea and malabsorption. 1, 3 This gastrointestinal involvement with Giardia lamblia is characteristic of antibody deficiency disorders like XLA. 4
Family history of sepsis death strongly suggests X-linked inheritance, which is seen in XLA affecting maternal male relatives. 1, 2
Why Not the Other Options
Omenn's syndrome (Option A) is ruled out because it presents in early infancy (first few months) with erythroderma, hepatosplenomegaly, lymphadenopathy, and failure to thrive—none of which match this presentation. 5 Omenn's syndrome would show lymphadenopathy, not absent lymph nodes.
Severe Combined Immunodeficiency/SCID (Option C) is excluded because SCID presents with opportunistic infections (Pneumocystis, fungal, viral) within the first 3-6 months of life, not just bacterial respiratory and gastrointestinal infections. 1, 2 The pattern of bacterial infections without opportunistic infections supports agammaglobulinemia rather than SCID. 1 Additionally, patients with XLA often survive longer with recurrent but treatable bacterial infections, whereas SCID is rapidly fatal without treatment. 2
Diagnostic Confirmation Required
Order immediately:
Serum immunoglobulin levels (IgG, IgA, IgM) - expect very low or undetectable levels of all three classes. 2, 6
Flow cytometry for CD19+ B cells - expect <2% of lymphocytes (virtually absent B cells). 1, 2
T-cell enumeration - expect normal numbers and function, distinguishing XLA from SCID. 2
Critical Management Priorities
Initiate treatment immediately upon diagnosis without waiting for genetic confirmation. 1
Start lifelong IgG replacement therapy (400-600 mg/kg every 3-4 weeks intravenously or weekly subcutaneously) to prevent further infections and complications. 2
Aggressive antimicrobial therapy for current infections, with consideration of antibiotic prophylaxis for breakthrough infections. 2
Monitor for enteroviral CNS infections (particularly ECHO virus), which are specific life-threatening complications of XLA. 1, 2, 6
Careful pulmonary monitoring to prevent bronchiectasis, which develops in 10-20% of patients despite treatment. 1
Common Pitfalls to Avoid
Do not delay diagnosis waiting for B-cell enumeration if immunoglobulin levels are in the agammaglobulinemic range—the clinical picture is sufficient to initiate treatment. 1 Earlier diagnosis and treatment initiation are associated with reduced lower respiratory tract infections and mortality; for every year increase in age at start of therapy, the odds of experiencing a lower respiratory tract infection increase by 21.6%. 1
Do not confuse with transient hypogammaglobulinemia of infancy, which would not present with undetectable levels of all three immunoglobulin classes and absent lymph nodes. 1