A 28-year-old woman with recurrent vulvovaginal candidiasis and poor wound healing is found to have absent circulating T lymphocytes on flow cytometry. ADA enzyme activity is undetectable in erythrocyte lysate. The underlying pathogenesis involves accumulation of which toxic metabolite in lymphocytes?
- A Hypoxanthine and xanthine from purine degradation
- B Orotic acid causing pyrimidine starvation of lymphocytes
- C Deoxyadenosine (dAdo) and dATP causing lymphocyte apoptosis ✓
- D Phenylalanine accumulation causing lymphocyte dysfunction
Explanation
Adenosine deaminase (ADA) deficiency is the most common cause of autosomal recessive severe combined immunodeficiency (SCID). ADA normally deaminates adenosine to inosine and deoxyadenosine to deoxyinosine. In ADA deficiency, deoxyadenosine accumulates and is phosphorylated to dATP by deoxynucleoside kinases — dATP is particularly toxic to lymphocytes (especially T cells) because it inhibits ribonucleotide reductase (blocking DNA synthesis) and activates apoptotic pathways. Both T and B cells are affected (T−B−NK− SCID phenotype). Treatment options include PEG-ADA enzyme replacement therapy, hematopoietic stem cell transplant (HSCT), or gene therapy.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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