Adenosine deaminase (ADA) deficiency causes SCID primarily because:

• A ADA deficiency blocks purine de novo synthesis, reducing ATP for lymphocyte proliferation
• B Deoxyadenosine accumulates, is phosphorylated to dATP, which inhibits ribonucleotide reductase and is toxic to lymphocytes ✓
• C Adenosine accumulates and activates adenosine receptors, inducing lymphocyte apoptosis
• D ADA deficiency leads to xanthine oxidase inhibition and purine accumulation in all cells equally

Explanation

ADA converts adenosine and deoxyadenosine to inosine and deoxyinosine respectively. In ADA-SCID, deoxyadenosine accumulates and is phosphorylated by deoxycytidine kinase (active in lymphocytes) to dATP. Elevated dATP allosterically inhibits ribonucleotide reductase, blocking DNA synthesis and causing lymphocyte apoptosis. T cells are more sensitive than B cells. This toxicity is lymphocyte-specific because of their high deoxycytidine kinase activity.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.