Immunology · Year 2 · from Immunology
Case 1: Severe Combined Immunodeficiency (SCID)
Patient Demographics
- Age: 4 months old
- Sex: Male
- Ethnicity: Caucasian
Chief Complaint
Failure to thrive and recurrent infections
History of Present Illness
A 4-month-old male infant is referred to pediatric immunology after being hospitalized for Pneumocystis jirovecii pneumonia (PJP). He has had persistent oral thrush since 2 weeks of age despite multiple courses of nystatin. His mother reports chronic diarrhea and poor weight gain. He was born full-term with no complications. Newborn screening was not available for SCID in his birth state.
Past Medical History
- Oral thrush since 2 weeks of age
- Chronic diarrhea starting at 2 months
- Admitted twice for respiratory infections
- Pneumocystis jirovecii pneumonia (current)
Birth History
- Full-term, uncomplicated vaginal delivery
- Birth weight: 3.4 kg (50th percentile)
- No newborn SCID screening performed
Family History
- Parents are non-consanguineous
- Maternal uncle died at 5 months of age from "lung infection"
Physical Examination
- General: Wasted, ill-appearing infant, visibly malnourished
- Vital Signs: T 38.2C, HR 160, RR 55, SpO2 88% on room air
- Weight: 4.5 kg (<3rd percentile, was 50th at birth)
- HEENT: Oral thrush coating tongue and buccal mucosa, NO visible tonsils
- Lymphatics: NO palpable lymph nodes
- Lungs: Bilateral crackles, increased work of breathing
- Abdomen: No hepatosplenomegaly
- Skin: No rashes, no evidence of graft-versus-host disease
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 3,200/uL | 6,000-17,500/uL |
| Absolute lymphocyte count | 200/uL | 3,000-9,500/uL |
| CD3+ T cells | 15/uL | 2,500-5,600/uL |
| CD4+ T cells | 8/uL | 1,600-4,000/uL |
| CD8+ T cells | 5/uL | 560-1,700/uL |
| CD19+ B cells | 850/uL | 300-2,000/uL |
| CD16+56+ NK cells | 8/uL | 170-1,100/uL |
| IgG | 180 mg/dL (maternal) | 141-930 mg/dL |
| IgA | <5 mg/dL | 8-74 mg/dL |
| IgM | <10 mg/dL | 26-210 mg/dL |
| TREC levels | Undetectable | Present |
| Genetic testing | IL2RG mutation | -- |
Clinical Image
Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Human_tongue_infected_with_oral_candidiasis.jpg). Public domain.
Diagnosis
X-linked Severe Combined Immunodeficiency (X-SCID) due to IL2RG (common gamma chain) mutation, presenting with T-B+NK- phenotype.
Discussion
SCID represents the most severe form of primary immunodeficiency, characterized by profound defects in T cell development. X-linked SCID is caused by mutations in IL2RG, which encodes the common gamma chain shared by receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. IL-7 signaling is essential for T cell development, and IL-15 is required for NK cell development, explaining the T-B+NK- phenotype. B cells develop but cannot function without T cell help.
Key features distinguishing this case:
- Profound lymphopenia with markedly reduced T cells
- Absent T cell and NK cells with preserved B cell numbers (T-B+NK-)
- Opportunistic infection (PJP) indicates severe cellular immunodeficiency
- Maternal uncle's death suggests X-linked inheritance
- Absent lymphoid tissue (tonsils, lymph nodes)
Treatment
- Immediate: Treat PJP with TMP-SMX, prophylaxis against infections, IVIG replacement
- Isolation: Strict infection precautions, avoid live vaccines
- Definitive therapy: Hematopoietic stem cell transplantation (HSCT) - outcomes are best when performed before 3.5 months of age and before infections develop
- Gene therapy: Now FDA-approved for X-SCID as an alternative to HSCT
Note: This case highlights the importance of newborn SCID screening using the TREC assay, now universal in all US states.