Adenosine deaminase (ADA) deficiency causes SCID by accumulation of which toxic metabolite selectively lethal to lymphocytes?

• A Xanthosine monophosphate (XMP)
• B Deoxyadenosine triphosphate (dATP) accumulating intracellularly, inhibiting ribonucleotide reductase ✓
• C Uric acid precipitating in lymph nodes, causing lymphocytic necrosis
• D S-adenosylhomocysteine accumulation inhibiting methyltransferases in lymphocytes

Explanation

ADA deficiency leads to accumulation of deoxyadenosine, which is phosphorylated to dATP in lymphocytes. dATP accumulates to high concentrations and inhibits ribonucleotide reductase (the enzyme converting ribonucleotides to deoxyribonucleotides), impairing DNA synthesis and causing apoptosis. Lymphocytes (especially T cells) are uniquely susceptible because they lack purine nucleoside phosphorylase activity to degrade deoxyadenosine via an alternate route. This is the basis for gene therapy targeting ADA-SCID.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.