A 9-year-old girl has splenomegaly, autoimmune hemolytic anemia, and lymphadenopathy. Biopsy shows florid lymphoproliferation. Flow cytometry reveals an expanded population of CD3-positive, CD4-negative, CD8-negative T cells bearing alpha-beta T cell receptors. The most likely underlying genetic defect is:

• A Homozygous deletion of the AIRE gene
• B Mutation of the SH2DIA (SAP) gene on the X chromosome
• C Mutation of the FAS gene impairing apoptosis of activated lymphocytes ✓
• D Mutation of the ATM gene causing chromosomal instability

Explanation

Autoimmune lymphoproliferative syndrome results from FAS (CD95) mutations that prevent apoptosis of activated lymphocytes after an immune response. The hallmark is accumulation of double-negative alpha-beta T cells (CD3 positive, CD4 and CD8 negative), together with splenomegaly and autoimmune cytopenias. AIRE defects cause APS-1 with mucocutaneous candidiasis and endocrinopathies, SAP defects cause X-linked lymphoproliferative disease triggered by EBV, and ATM defects cause ataxia telangiectasia.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.