Severe Combined Immunodeficiency (SCID)
This 9-month-old infant has Severe Combined Immunodeficiency (SCID), a life-threatening emergency requiring immediate hematopoietic stem cell transplantation (HSCT). 1
Clinical Presentation Matches SCID
The constellation of findings is pathognomonic for SCID:
- Chronic diarrhea and failure to thrive are the classic initial presentations of SCID in infants 1
- Recurrent pneumonia and otitis media indicate complete absence of specific immunity with extreme susceptibility to all pathogens 1
- Panhypogammaglobulinemia (low IgG, IgA, and IgM) results from lack of T-cell help and intrinsic B-cell dysfunction 1
- Low B-cell subtypes with leukopenia confirms the combined T- and B-cell defect characteristic of SCID 1
Why This is SCID and Not Other Diagnoses
X-linked agammaglobulinemia (Bruton's) is excluded because it presents with absent or extremely low B cells (<2%), whereas this patient has low but detectable B-cell subtypes 1
Common Variable Immunodeficiency (CVID) is excluded because CVID cannot be diagnosed before age 4 years, and this infant's presentation at 9 months with severe combined deficiency points to SCID 1, 2
Transient hypogammaglobulinemia of infancy is excluded because the severity of infections, chronic diarrhea, and low WBC count indicate true immunodeficiency rather than a benign developmental delay 3
Immunophenotyping Determines SCID Subtype
The specific genetic defect depends on lymphocyte phenotyping:
- T-B- SCID (39% of cases): Most commonly caused by RAG1/2 defects, presents with absent T and B cells 4
- T-B+ SCID (28% of cases): Commonly caused by IL2RG (X-linked) or JAK3 defects, presents with absent T cells but present B cells 4
- Additional testing needed: Flow cytometry for CD3, CD4, CD8, CD19, and NK cells; T-cell proliferation to mitogens; and genetic testing to identify the specific molecular defect 1
Immediate Management Protocol
This is an urgent medical emergency—SCID infants can succumb to severe infection at any time, and outcomes are dramatically improved by earliest possible intervention. 1
Immediate Actions Required:
- Initiate IgG replacement therapy immediately with intravenous immunoglobulin (IVIG) to provide passive immunity 1
- Start antimicrobial prophylaxis: Trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia (PCP) prevention 5, 6
- Implement protective isolation from all infectious exposures, including avoiding live vaccines 5
- Treat active infections aggressively with broad-spectrum antimicrobials 1
Definitive Treatment:
- Urgent referral for HSCT evaluation—this is the only curative therapy and should be pursued as quickly as possible 1
- Gene therapy may be available for specific SCID subtypes (e.g., ADA-SCID, X-linked SCID) 7
Critical Pitfalls to Avoid
Do not wait for genetic confirmation before initiating treatment—the clinical and laboratory picture is sufficient to begin supportive care and HSCT evaluation 1
Do not administer live vaccines (rotavirus, BCG, MMR, varicella) as they can cause disseminated vaccine-strain infections in SCID patients 5
Do not use non-irradiated blood products—all blood products must be irradiated to prevent transfusion-associated graft-versus-host disease 1
Do not delay HSCT referral—survival rates exceed 90% when HSCT is performed before 3.5 months of age and before serious infections develop, but drop significantly with delays 7, 4