Chediak–Higashi is one of those “you either remember it instantly or you blank” immunodeficiencies. The good news: Step questions usually test the same few clues—partial albinism + recurrent pyogenic infections + giant granules—so a clean acronym can get you the point in seconds.
The Acronym Trick: C.H.E.D.I.A.K.
Use C.H.E.D.I.A.K. as a rapid checklist for classic features:
- C = Clumsy chemotaxis (neutrophils don’t migrate well)
- H = Hypopigmentation (partial albinism, light hair/skin)
- E = ENLARGED granules (giant lysosomal granules in granulocytes/platelets)
- D = Defective degranulation (impaired phagolysosome fusion)
- I = Infections (recurrent pyogenic, classically Staph aureus and Strep pyogenes)
- A = Axonal neuropathy (progressive peripheral neuropathy can show up in vignettes)
- K = Killer cells impaired (↓ NK cell function)
One-liner: AR defect in LYST → failed phagolysosome fusion → giant granules + recurrent pyogenic infections + partial albinism.
The “Picture in Your Head” Mnemonic (Visual)
Imagine a “CHeeDy” leopard (cheetah) with:
- Patchy pale fur → partial albinism
- Stuffed, oversized “granule” pockets → giant granules
- Can’t “kill” prey well → ↓ NK cell function
- Keeps getting skin infections → recurrent pyogenic infections
If you can see the pale cheetah with huge pockets who can’t kill, you can reconstruct the diagnosis.
What’s Actually Broken? (High-Yield Pathophys)
Core defect
- Gene: LYST mutation
- Inheritance: Autosomal recessive
- Mechanism: defective lysosomal trafficking → impaired fusion of phagosomes with lysosomes
- Net effect: poor intracellular killing + abnormal granule formation
Why the classic findings happen
- Giant granules: lysosomes can’t traffic/fuse normally → enlarged cytoplasmic granules in neutrophils/other granulocytes (and platelets).
- Pyogenic infections: neutrophils can ingest but can’t finish the job efficiently → recurrent Staph/Strep.
- Partial albinism: melanosome trafficking is also a lysosome-related process → hypopigmentation.
- Neurologic issues: progressive peripheral neuropathy can be tested as a “bonus clue.”
Step-Style Clues You’re Expected to Recognize
Buzzwords in the stem
- “Partial albinism” + recurrent infections
- “Pyogenic bacteria” (especially S. aureus, S. pyogenes)
- “Giant granules” in granulocytes on peripheral smear
- Sometimes: peripheral neuropathy or nystagmus
Rapid Comparison Table (Because Test Writers Love Mix-Ups)
| Disorder | Key clue | What’s wrong | Infections/features |
|---|---|---|---|
| Chediak–Higashi | Partial albinism + giant granules | LYST mutation → ↓ phagolysosome fusion | Pyogenic (Staph/Strep), ↓ NK function, neuropathy |
| CGD | Abnormal DHR, catalase+ infections | NADPH oxidase defect | S. aureus, Serratia, Nocardia, Aspergillus |
| Griscelli | Partial albinism but no giant granules | Rab27A (vesicle trafficking) | Immunodeficiency + neuro; differs on smear |
| Hermansky–Pudlak | Albinism + bleeding | Platelet dense body defect | Bleeding + pulmonary fibrosis; not classic pyogenic pattern |
Ultra-Quick Recall (What to say in 5 seconds)
Chediak–Higashi = AR LYST defect → failed phagolysosome fusion → giant granules, partial albinism, recurrent staph/strep infections, ↓ NK cells.