A 3-year-old boy has recurrent pyogenic infections (Staph aureus, Streptococcal) since infancy. Absolute lymphocyte count is normal. IgG and IgA are severely reduced, IgM is elevated (1200 mg/dL). CD19+ B cells are present in normal numbers. What is the most likely diagnosis?

• A X-linked agammaglobulinemia (XLA — Bruton's disease)
• B Common variable immunodeficiency (CVID)
• C X-linked Hyper-IgM syndrome (CD40 ligand deficiency on T cells, prevents B-cell class switching) ✓
• D Selective IgA deficiency

Explanation

X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in TNFSF5 (CD40L, CD154) on T helper cells. Without CD40L–CD40 interaction, B cells cannot undergo class switch recombination from IgM to IgG/IgA/IgE, resulting in markedly elevated IgM with severely decreased IgG, IgA, IgE, despite normal B-cell numbers. XLA (Bruton's) presents with absent B cells (BTK mutation). CVID affects older children/adults with late-onset hypogammaglobulinemia and normal/reduced IgM. Selective IgA deficiency has isolated low IgA with normal IgG and IgM.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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