Learning Objective:
Identify primary phagocyte dysfunction disorders, their molecular defects, clinical presentations, and key laboratory findings.
Phagocyte Dysfunction Disorders
Leukocyte adhesion deficiency (LAD) type 1
Defect
Autosomal recessive LFA-1 (CD18) integrin defect → impaired migration and chemotaxis
Clinical features
Late separation of the umbilical cord (>30 days), recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing
Lab findings
↑ Neutrophils in blood, absence of neutrophils at infection sites
Chédiak-Higashi syndrome
Defect
Autosomal recessive defect in the LYST gene → impaired phagosome-lysosome fusion
Clinical features
PLAIN mnemonic: Progressive neurodegeneration, Lymphohistiocytosis, partial Albinism, recurrent pyogenic Infections, peripheral Neuropathy
Lab findings
Giant granules in granulocytes and platelets, pancytopenia, and mild coagulation defects
Chronic granulomatous disease (CGD)
Defect
Defective NADPH oxidase → ↓ reactive oxygen species → impaired respiratory burst; X-linked most common
Clinical features
Recurrent infections with catalase-positive organisms (S. aureus, Serratia, Nocardia, Pseudomonas), and granuloma formation
Lab findings
Abnormal dihydrorhodamine (DHR) flow cytometry (↓ green fluorescence); nitroblue tetrazolium (NBT) test fails to turn blue
Summary Table
| Disease | Defect | Clinical Features | Key Findings / Lab |
|---|---|---|---|
| Leukocyte adhesion deficiency (LAD) type 1 | Autosomal recessive LFA-1 (CD18) integrin defect → impaired migration and chemotaxis | Late separation of the umbilical cord (>30 days), recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing | ↑ Neutrophils in blood, absence of neutrophils at infection sites |
| Chédiak-Higashi syndrome | Autosomal recessive defect in the LYST gene → impaired phagosome-lysosome fusion | PLAIN mnemonic: Progressive neurodegeneration, Lymphohistiocytosis, partial Albinism, recurrent pyogenic Infections, peripheral Neuropathy | Giant granules in granulocytes and platelets, pancytopenia, and mild coagulation defects |
| Chronic granulomatous disease (CGD) | Defective NADPH oxidase → ↓ reactive oxygen species → impaired respiratory burst; X-linked most common | Recurrent infections with catalase-positive organisms (S. aureus, Serratia, Nocardia, Pseudomonas), and granuloma formation | Abnormal dihydrorhodamine (DHR) flow cytometry (↓ green fluorescence); nitroblue tetrazolium (NBT) test fails to turn blue |
High-Yield Mnemonics / Tips
- LAD: Late cord separation, Absent pus, Defective migration
- Chédiak-Higashi / PLAIN: Progressive neurodegeneration, Lymphohistiocytosis, Albinism, Infections, Neuropathy
- CGD / “granny’s cats keep her positive”: Catalase-positive organisms → recurrent infections; NADPH oxidase defect
