X-linked Agammaglobulinemia (XLA)
The correct diagnosis is A. X-linked agammaglobulinemia (XLA), based on the constellation of recurrent bacterial infections, low B cells, normal T cells, and a family history affecting a male sibling. 1, 2
Diagnostic Reasoning
The clinical presentation definitively points to agammaglobulinemia rather than the other options:
- Low B cells with normal T cells is the hallmark laboratory finding that distinguishes agammaglobulinemia from other immunodeficiencies 1
- X-linked inheritance pattern is strongly suggested by the affected male sibling who died from a similar condition, while the female siblings (ages 3 and 5) remain healthy 1, 2
- Recurrent bacterial infections including pneumonia fits the classic presentation of agammaglobulinemia, which typically manifests with recurrent respiratory tract infections from encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae 1, 2
Why Other Options Are Incorrect
Ataxia telangiectasia (Option B) would present with both B and T cell abnormalities, progressive cerebellar ataxia, telangiectasias, and elevated alpha-fetoprotein—none of which are described here 1
Chronic granulomatous disease (Option C) involves phagocytic cell defects with normal B and T cell counts, presenting with severe pyogenic bacterial and fungal infections of skin and viscera, not isolated low B cells 1
Hyper IgE syndrome (Option D) would show elevated IgE levels (not low B cells), characteristic facial features, eczema, and recurrent staphylococcal skin abscesses 1
Key Diagnostic Features of XLA
- Approximately 85% of agammaglobulinemia cases are X-linked due to mutations in the Bruton tyrosine kinase (BTK) gene 1, 2
- Peripheral blood CD19+ B-cell counts <2% is characteristic and diagnostic 1, 2
- Serum immunoglobulin levels typically show IgG <100 mg/dL, IgM <20 mg/dL, and IgA <10 mg/dL 1
- Physical examination usually reveals absent or markedly decreased tonsils and lymph nodes, distinct from other antibody deficiencies 1
Critical Clinical Pitfall
Do not delay diagnosis waiting for complete immunoglobulin quantification if B-cell enumeration shows <2% CD19+ cells—the combination of low B cells with normal T cells in a male child with recurrent bacterial infections is sufficient to initiate treatment 2. Some XLA patients can have detectable immunoglobulin levels early in disease, which can mislead clinicians 3, 4, 5, but the B-cell count remains the most reliable diagnostic marker.
Immediate Management Priorities
Agammaglobulinemia must be managed aggressively with antimicrobials, IgG replacement therapy, and careful pulmonary monitoring 1, 2. This is a medical urgency because:
- Initiate intravenous immunoglobulin (IVIG) replacement immediately to prevent further infections and life-threatening complications 2, 6
- Monitor specifically for enteroviral infections, particularly CNS ECHO virus infections, which are unique complications of agammaglobulinemia and can cause serious morbidity or mortality 1, 2
- Maintain aggressive antimicrobial therapy for any suspected bacterial infection, as these patients are at high risk for overwhelming sepsis 1, 2