A male infant presents with severe watery diarrhea, eczematous dermatitis, early-onset type 1 diabetes, and recurrent infections. Biopsy of the gut shows villous atrophy with minimal plasma cell infiltrate. Sequencing reveals a mutation in FOXP3. The fundamental immunological consequence of this mutation is:

• A Absence of functional CD4+CD25+ regulatory T cells ✓
• B Failure of V(D)J recombination in developing lymphocytes
• C Defective oxidative burst in phagocytes
• D Impaired thymic epithelial development causing absent negative selection

Explanation

FOXP3 is the master transcription factor for CD4+CD25+ regulatory T cells. Its loss causes IPEX syndrome (immunodysregulation polyendocrinopathy enteropathy X-linked), in which autoreactive effector T cells escape regulation, producing autoimmunity against endocrine organs, enteropathy, and eczema. V(D)J recombination defects cause SCID, NADPH oxidase defects cause chronic granulomatous disease, and impaired negative selection describes AIRE-related APS-1, none of which match the multi-organ autoimmune phenotype here.

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.