X-linked (Bruton) Agammaglobulinemia is the Most Likely Diagnosis
The combination of undetectable IgG, IgM, and IgA levels with normal T-cell counts in an infant with recurrent bacterial infections (pneumonia, otitis media) is diagnostic of agammaglobulinemia, most commonly X-linked agammaglobulinemia (XLA). 1
Diagnostic Reasoning
Key Distinguishing Features
The critical laboratory finding that differentiates these two conditions is normal T-cell counts:
Agammaglobulinemia is characterized by very low or undetectable serum immunoglobulin concentrations (IgG usually <100 mg/dL, IgM <20 mg/dL, IgA <10 mg/dL) with normal T-cell numbers and function 1
SCID always affects T cells as the hallmark immunologic abnormality, with very low or absent T-cell counts and profoundly reduced proliferation to mitogens and antigens 2
Clinical Presentation Matches Agammaglobulinemia
The infant's presentation is classic for agammaglobulinemia:
Recurrent bacterial respiratory tract infections (pneumonia, otitis media) typically present in the first 2 years of life, with Streptococcus pneumoniae and Haemophilus influenzae as the most common organisms 1
Chronic diarrhea can occur in agammaglobulinemia, though less commonly than respiratory infections 3
The pattern of bacterial infections without opportunistic infections (which would suggest T-cell dysfunction in SCID) supports agammaglobulinemia 1
Why Not SCID?
SCID would present with:
Abnormal T-cell counts (very low or absent), which this patient does not have 2
Opportunistic infections including Pneumocystis jirovecii pneumonia (PCP), severe viral infections, and fungal infections due to T-cell dysfunction 2
Earlier and more severe presentation with failure to thrive, chronic diarrhea from opportunistic pathogens, and life-threatening infections in the first months of life 2
While B cells are often functionally impaired in SCID, the normal T-cell counts explicitly exclude this diagnosis 2
X-linked Agammaglobulinemia Specifics
Approximately 85% of agammaglobulinemia cases are X-linked (XLA) due to mutations in the BTK gene 1:
Peripheral blood CD19+ B-cell counts <2% is characteristic and should be confirmed 1
Absence of BTK protein in monocytes or platelets can be detected by Western blotting or flow cytometry 1
Family history of affected maternal male relatives (cousins, uncles, nephews) may be present, though sporadic cases are common 1, 4
Physical examination typically reveals absence of lymph nodes and tonsils, distinct from other antibody deficiencies 1
Immediate Management Priorities
Agammaglobulinemia should be managed aggressively with antimicrobials, IgG replacement, and careful attention to pulmonary status 1:
Initiate IgG replacement therapy immediately to prevent further infections and complications 1, 5, 3
Aggressive antimicrobial treatment for current infections and consideration of prophylactic antibiotics 1
Monitor for enteroviral infections, particularly CNS ECHO virus infections, which are specific complications of agammaglobulinemia 1
Avoid live viral vaccines (particularly oral polio vaccine, though this is no longer routinely used) due to risk of vaccine-strain infection 1, 5
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
Do not confuse with transient hypogammaglobulinemia of infancy, which would not present with undetectable levels of all three immunoglobulin classes 6
Do not assume SCID based solely on severe infections and hypogammaglobulinemia without checking T-cell counts 2
Recognize that some patients may not be diagnosed until after 5 years of age despite frequent infections, though most present in the first 2 years 1, 3