A 3-year-old girl has recurrent bacterial infections, normal B and T lymphocyte counts, normal serum immunoglobulins, but neutrophils fail to kill ingested bacteria. DHR (dihydrorhodamine flow cytometry) test shows absent fluorescence shift after PMA stimulation. Nitroblue tetrazolium (NBT) test is negative. What is the diagnosis and the underlying enzyme defect?
- A Chronic granulomatous disease (CGD) — deficiency of NADPH oxidase (gp91phox subunit in X-linked form) ✓
- B Leukocyte adhesion deficiency (LAD) — CD18 (beta-2 integrin) deficiency
- C Chediak-Higashi syndrome — giant azurophilic granule formation due to LYST protein mutation
- D Myeloperoxidase deficiency — unable to generate hypochlorous acid from H₂O₂
Explanation
Chronic granulomatous disease (CGD) is characterised by recurrent catalase-positive bacterial (Staphylococci, Klebsiella, Serratia, Aspergillus) infections with granuloma formation, despite normal neutrophil counts and immunoglobulins. The defect is in NADPH oxidase (a multicomponent system) — X-linked forms involve gp91phox (most common); autosomal recessive forms involve p47phox, p67phox, etc. NADPH oxidase generates the superoxide anion in the respiratory burst. DHR (dihydrorhodamine) fluorescence and NBT reduction both test NADPH oxidase function — absent/reduced result confirms CGD. LAD patients have normal respiratory burst but cannot migrate to infection sites; NBT would be normal.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.