A boy presents at age 6 months with recurrent Pneumocystis pneumonia and failure to thrive. T cell count is profoundly low; B cells are also absent. Adenosine deaminase (ADA) enzyme activity is absent in RBCs. The mechanism of lymphocyte death in ADA-SCID is:

• A Accumulation of deoxyadenosine and dATP, which are toxic to lymphocytes and induce apoptosis ✓
• B Failure of VDJ recombination due to RAG1/RAG2 deficiency
• C Defective IL-7 receptor gamma chain signaling blocking T-cell development
• D BTK mutation preventing B-cell maturation beyond pre-B stage

Explanation

ADA deficiency causes accumulation of deoxyadenosine and its phosphorylated form dATP, which are particularly toxic to lymphocytes (both T and B cells) because lymphocytes have high levels of deoxynucleoside kinases and low deoxyribonucleotidase activity. Accumulated dATP inhibits ribonucleotide reductase (blocking DNA synthesis) and induces apoptosis. This causes the profound combined T and B cell deficiency. RAG mutations and gamma-c chain defects cause SCID by different mechanisms.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.