Adenosine deaminase (ADA) deficiency causes SCID predominantly affecting T lymphocytes. The toxic metabolite responsible for lymphocyte death is:
- A Xanthosine monophosphate
- B dATP accumulation inhibiting ribonucleotide reductase ✓
- C Uric acid crystallization within lymphocytes
- D IMP accumulation blocking de novo purine synthesis
Explanation
In ADA deficiency, adenosine and deoxyadenosine cannot be deaminated to inosine/deoxyinosine. Deoxyadenosine is phosphorylated by deoxynucleoside kinases to dATP, which accumulates to high levels in lymphocytes (especially T cells, which have high deoxynucleoside kinase activity). Elevated dATP potently inhibits ribonucleotide reductase (which requires a balanced dNTP pool), blocking DNA synthesis and causing lymphocyte apoptosis. ADA enzyme replacement therapy (pegademase bovine) and gene therapy targeting this pathway have been developed. Uric acid crystallization (option C) is not the mechanism in ADA-SCID.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.