Chronic granulomatous disease (CGD)
– Aka NADPH oxidase deficiency
– Usually X-linked recessive (mostly boys)
– 1st enzyme of the respiratory burst; converts molecular O₂ → superoxide
– Recurrent infections with catalase (+) organisms: Serratia, Pseudomonas, Aspergillus, Candida, E. coli, Staph, H. pylori, Burkholderia
– ~50% of Qs use S. aureus; the rest use other organisms from list
– Results in ↓ ability to synthesize enough H₂O₂ to overwhelm catalase (+) organisms
– Diagnose with dihydrorhodamine test (tetrazolium blue assay = outdated/wrong if both listed on Step 1 NBME)
Myeloperoxidase (MPO) deficiency
– Autosomal recessive
– Last enzyme in respiratory burst; converts H₂O₂ → hydroxyl-halide radicals (bleach)
– Question stem often states inability to produce hydroxyl-halide radicals → answer is MPO deficiency
– Vignette may explicitly mention MPO deficiency → answer is “impaired conversion of hydrogen peroxide to hypochlorous acid”
– Usually presents with mixed Staph aureus + Candida infections
– a question: 6-year-old girl, AR, mixed S. aureus + Candida → MPO deficiency, not CGD
– Although CGD can show similar infections, ~70% of CGD is X-linked; AR CGD is milder and presents later
Leukocyte adhesion deficiency (LAD)
– Deficiency of CD18/LFA-1 integrin
– ↓ ability of WBCs to leave blood vessels → ↓ pus
– Classically: delayed separation of umbilical cord (~50% of Qs)
– Other half: “absent pus/neutrophils in the skin”
– Answer may be “defective leukocyte chemotaxis” instead of LAD
Chediak-Higashi syndrome
– Phagolysosomal fusion disorder with disrupted microtubule function
–Mutation in the LYST gene, which affects lysosomal trafficking.
– Impaired melanosome function → partial albinism / fairer skin than siblings
– Giant granules in phagocytes
Chediak-Higashi syndrome → oculocutaneous albinism + recurrent infections + neutropenia + giant neutrophil granules.
