A 2-year-old boy has recurrent sinopulmonary and viral infections. Immunophenotyping shows severely reduced CD4 and CD8 T cells with preserved B-cell numbers and near-normal immunoglobulin levels. Enzyme assay reveals deficient purine nucleoside phosphorylase. Why does this defect selectively impair T cells?
- A Accumulated deoxyguanosine is phosphorylated to dGTP, which inhibits ribonucleotide reductase in T cells ✓
- B Accumulated deoxyadenosine traps SAICAR in T-cell mitochondria
- C Loss of the enzyme blocks uric acid formation, poisoning rapidly dividing T cells
- D Defective salvage of guanine deprives T cells of GMP
Correct answer: A. Accumulated deoxyguanosine is phosphorylated to dGTP, which inhibits ribonucleotide reductase in T cells
Explanation
Without purine nucleoside phosphorylase, deoxyguanosine and guanosine accumulate. In T cells these are phosphorylated to dGTP, which allosterically inhibits ribonucleotide reductase and halts DNA synthesis. Deoxyadenosine accumulation is the mechanism in ADA deficiency, not PNP deficiency, and B cells are relatively spared because they lack high deoxynucleoside kinase activity.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.