Immunology · Year 2 · from Immunology
Case 1: X-Linked Agammaglobulinemia (Bruton's)
Patient Demographics
- Age: 18 months old
- Sex: Male
- Ethnicity: Caucasian
Chief Complaint
Recurrent ear infections and pneumonia
History of Present Illness
An 18-month-old boy is referred to pediatric immunology after his fourth episode of pneumonia. He has had multiple ear infections since 7 months of age, requiring at least 10 courses of antibiotics. He was healthy for the first 6 months of life. His current pneumonia was caused by Streptococcus pneumoniae. He has recovered normally from viral illnesses including RSV bronchiolitis.
Past Medical History
- First 6 months: No significant infections
- Bilateral otitis media: 12+ episodes since 7 months of age
- Pneumonia: 4 episodes (8 mo, 11 mo, 15 mo, current)
- Sinusitis: 3 episodes requiring antibiotics
- No history of opportunistic infections
Vaccination History
- Received routine vaccines including live vaccines (MMR at 12 months) without adverse events
Family History
- Maternal uncle died at age 3 from "recurrent infections"
- One healthy older sister
Physical Examination
- General: Small-appearing child, in mild respiratory distress
- Vital Signs: T 38.5C, HR 130, RR 32, SpO2 94% on room air
- Growth: Weight 10th percentile, Height 25th percentile
- HEENT: Bilateral TM erythema, tonsils not visible (absent)
- Lymphatics: No palpable lymph nodes (cervical, axillary, inguinal)
- Lungs: Decreased breath sounds right middle lobe, crackles
- Abdomen: No hepatosplenomegaly
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 12,500/uL | 6,000-17,500/uL |
| Lymphocytes | 45% | 40-70% |
| IgG | <20 mg/dL | 345-1236 mg/dL |
| IgA | <5 mg/dL | 14-159 mg/dL |
| IgM | <10 mg/dL | 43-207 mg/dL |
| CD19+ B cells | <1% (<0.1% of lymphocytes) | 14-33% |
| CD3+ T cells | Normal | -- |
| CD4+ T cells | Normal | -- |
| CD8+ T cells | Normal | -- |
| BTK protein | Absent (by flow cytometry) | Present |
| BTK gene | Pathogenic mutation | -- |
Clinical Image
Image for comparison showing normal tonsils; in XLA, tonsils are characteristically absent. Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Grade_1_tonsils.jpg). Licensed under CC BY 3.0.
Diagnosis
X-Linked Agammaglobulinemia (Bruton's Agammaglobulinemia) due to BTK gene mutation.
Discussion
XLA results from mutations in BTK (Bruton's tyrosine kinase), which is essential for signaling through the pre-B cell receptor. Without BTK, B cell development arrests at the pro-B to pre-B cell transition, resulting in:
- Virtual absence of mature B cells in peripheral blood (<1%)
- Profoundly low immunoglobulin levels (all classes)
- Absent lymphoid tissue (tonsils, lymph nodes) because B cells are required to populate these structures
Key clinical features:
- Onset after 6 months (when maternal IgG wanes)
- Recurrent bacterial infections with encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae)
- Normal recovery from most viral infections (T cell immunity intact, though enteroviruses can cause chronic infection)
- Absent tonsils and lymph nodes on physical exam - important diagnostic clue
- X-linked inheritance (maternal uncle affected)
Distinguishing from CVID:
- XLA: Absent B cells, childhood onset, absent lymphoid tissue
- CVID: Normal B cells (dysfunction), later onset, lymphoid tissue present
Treatment
- Immunoglobulin replacement: IVIG or SCIG - lifelong, with goal trough IgG >500 mg/dL
- Aggressive antibiotic therapy: For breakthrough infections
- Avoid live vaccines: Although T cell-mediated immunity is normal, live viral vaccines should be avoided
- Prophylactic antibiotics: May be considered for patients with recurrent infections despite adequate Ig replacement
- Monitoring: Watch for chronic enteroviral infection (meningoencephalitis), bronchiectasis