A 3-year-old boy has severe combined immunodeficiency (SCID), lymphopenia, and no B or T cells. Enzyme assay shows absent adenosine deaminase (ADA) activity. The toxic metabolite that accumulates and kills lymphocytes is:

• A Hypoxanthine
• B Uric acid
• C Orotic acid
• D Deoxyadenosine triphosphate (dATP) ✓

Explanation

ADA deficiency allows deoxyadenosine to accumulate; lymphocytes have high deoxynucleoside kinase and low 5'-nucleotidase activity, so deoxyadenosine is phosphorylated to dATP, which accumulates to toxic levels and inhibits ribonucleotide reductase, depleting dNTP pools needed for DNA synthesis, causing lymphocyte apoptosis. Hypoxanthine accumulation causes gout (HGPRT deficiency). Orotic acid accumulates in OTC deficiency and orotic aciduria.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.