A 3-year-old boy has severe, life-threatening infections with encapsulated bacteria, fungi, and Pneumocystis jirovecii. Flow cytometry shows absent T and B lymphocytes with NK cells present. This pattern is most consistent with:

• A X-linked SCID due to IL2RG (gamma chain) mutation impairing signaling through IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 receptors (T-B+NK- is IL2RG; T-B-NK+ is RAG1/2)
• B RAG1 or RAG2 deficiency causing failure of V(D)J recombination with absent T and B but preserved NK cells ✓
• C Adenosine deaminase deficiency causing non-selective lymphocyte toxicity
• D X-linked agammaglobulinemia (Bruton) with absent B cells but normal T cells

Explanation

The pattern T-B-NK+ SCID (absent T and B lymphocytes with preserved NK cells) is characteristic of RAG1 or RAG2 gene deficiency. RAG1/RAG2 form the V(D)J recombinase that is essential for assembling functional T-cell receptor and immunoglobulin gene segments — their absence prevents maturation of both T and B lymphocytes. NK cells do not require RAG-mediated rearrangement so they are spared. X-linked SCID (IL2RG) typically shows T-B+NK- pattern. ADA deficiency causes T-B-NK- (all lymphocytes affected by toxic deoxyadenosine accumulation).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.