Severe combined immunodeficiency (SCID)
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A 4-month-old with failure to thrive has recurrent severe infections including pneumonia, chronic diarrhea, and oral candidiasis. Lymphocyte count is very low.
Multiple genes
- XLR: IL2RG (common gamma chain) - most common
- AR: ADA, RAG1, RAG2, JAK3, others
Types by lymphocyte phenotype:
- T-B+NK- (X-linked, IL2RG)
- T-B-NK+ (RAG1/2)
- T-B-NK- (ADA)
- Severe recurrent infections (bacterial, viral, fungal, opportunistic)
- Failure to thrive
- Absent/dysfunctional T cells
- Absent thymus on X-ray
- On RUSP (TREC-based screening)
- Newborn screening: low/absent T-cell receptor excision circles (TRECs) flags affected infants before symptom onset
- Lymphocyte subset flow cytometry (CD3 T cells, CD19 B cells, CD16/56 NK cells) defines the T-B-NK phenotype and points to the genetic subtype
- Confirmatory molecular testing (IL2RG, ADA, RAG1/RAG2, JAK3, others); ADA deficiency confirmed by absent enzyme activity and elevated dATP
- Workup is urgent: SCID is a pediatric emergency
- HSCT (curative), gene therapy (for some types), avoid live vaccines
SCID presents earlier than Bruton's: SCID presents on newborn screen (decreased TRECs) or within the first few weeks of life, versus 5-6 months for Bruton's agammaglobulinemia. Both have absent thymic shadow on CXR (like DiGeorge).
ADA deficiency causes AR SCID: Adenosine deaminase normally degrades adenosine and deoxyadenosine to inosine. Increased dATP is lymphotoxic, destroying both B and T cells (T-B-NK- phenotype).