Table V.
Congenital defects of phagocyte number, function, or both
| Disease | Affected cells | Affected function | Associated features | Inheritance | Gene defects-presumed pathogenesis | |
|---|---|---|---|---|---|---|
| 1.–3. | Severe congenital neutropenias | N | Myeloid Differentiation | Subgroup with myelodysplasia | AD | ELA2: mistrafficking of elastase |
| N | Myeloid Differentiation | B/T lymphopenia | AD | GFI1: repression of elastase | ||
| N | Myeloid Differentiation | G-CSF refractory neutropenia | AD | G-CSFR | ||
| 4. | Kostmann Disease | N | Myeloid Differentiation | AR | HAX1:control of apoptosis | |
| 5. | Cyclic neutropenia | N | ? | Oscillations of other leukocytes and platelets | AD | ELA2: mistrafficking of elastase |
| 6. | X-linked neutropenia/myelodysplasia | N + M | ? | Monocytopenia | XL | WASP: Regulator of actin cytoskeleton (loss of autoinhibition) |
| 7. | P14 deficiency | N+L | Endosome biogenesis | Neutropenia | AR | MAPBPIP: Endosomal adaptor protein 14 |
| Mel | Hypogammaglobulinemia | |||||
| ↓CD8 cytotoxicity | ||||||
| Partial albinism | ||||||
| Growth failure | ||||||
| 8. | Leukocyte adhesion deficiency | N + M | Adherence | Delayed cord separation Skin ulcers | AR | INTGB2: Adhesion protein |
| type 1 | L + NK | Chemotaxis | Periodontitis | |||
| Endocytosis | Leukocytosis | |||||
| T/NK cytotoxicity | ||||||
| 9. | Leukocyte adhesion deficiency | N + M | Rolling | LAD type 1 features | AR | FUCT1 GDP-Fucose transporter |
| type 2 | Chemotaxis | plus hh-blood group and mental retardation | ||||
| 10. | Leukocyte adhesion deficiency | N + M | Adherence | LAD type 1 plus bleeding tendency | AR | Cal DAG-GEFI: |
| type 3 | L + NK | defective Rap1-activation of β1–3 integrins | ||||
| 11. | Rac 2 deficiency | N | Adherence | Poor wound healing | AD | RAC2: Regulation of actin cytoskeleton |
| Chemotaxis | Leukocytosis | |||||
| O2− production | ||||||
| 12. | β-actin deficiency | N + M | Motility | Mental retardation | AD | ACTB: Cytoplasmic Actin |
| Short stature | ||||||
| 13. | Localized juvenile Periodontitis | N | Formylpeptide induced chemotaxis | Periodontitis only | AR | FPR1: Chemokine receptor |
| 14. | Papillon-Lefèvre Syndrome | N + M | Chemotaxis | Periodontitis, Palmoplantar hyperkeratosis | AR | CTSC: Cathepsin C activation of serine proteases |
| 15. | Specific granule deficiency | N | Chemotaxis | N with bilobed nuclei | AR | C/EBPE: myeloid transcription factor |
| 16. | Shwachman-Diamond Syndrome | N | Chemotaxis | Pancytopenia, exocrine pancreatic insufficiency Chondrodysplasia | AR | SBDS |
| 17. | X-linked chronic granulomatous disease (CGD) | N + M | Killing (faulty O2− production) | Subgroup: McLeod phenotype | XL | CYBB: Electron transport protein (gp91phox) |
| 18.–20. | Autosomal CGD’s | N + M | Killing (faulty O2− production) | AR | CYBA: Electron transport protein (p22phox) | |
| NCF1: Adapter protein (p47phox) | ||||||
| NCF2: Activating protein (p67phox) | ||||||
| 21. | Neutrophil G-6PD deficiency | N + M | Killing (faulty O2 − production) | Hemolytic anemia | XL | G-6PD: NADPH generation |
| 22. | IL-12 and IL-23 receptor β1 chain deficiency | L + NK | IFN-γ secretion | Susceptibility to Mycobacteria and Salmonella | AR | IL-12Rβ1: IL-12 and IL-23 receptor β1 chain |
| 23. | IL-12p40 deficiency | M | IFN-γ secretion | Susceptibility to Mycobacteria and Salmonella | AR | IL-12p40 subunit of IL12/IL23: IL12/IL23 production |
| 24. | IFN-γ receptor 1 deficiency | M + L | IFN-γ binding and signaling | Susceptibility to Mycobacteria and Salmonella | AR, AD | IFN-γR1: IFN-γR binding chain |
| 25. | IFN-γ receptor 2 deficiency | M + L | IFN-γ signaling | Susceptibility to Mycobacteria and Salmonella | AR | IFN-γR2: IFN-γR signaling chain |
| 26. | STAT1 deficiency (2 forms) | M + L | IFN α/β/γ signaling | Susceptibility to Mycobacteria, Salmonella and viruses | AR | STAT1 |
| IFN-γ signaling | Susceptibility to Mycobacteria and Salmonella | AD | STAT1 |
AD, Inherited form of IFN-Rγ1 deficiency or of STAT1 deficiency is due to dominant negative mutations; XL, X-linked inheritance; AR, autosomal recessive inheritance; N, neutrophils; M, monocytes-macrophages; L, lymphocytes; NK, natural killer cells; Mel, melanocytes; STAT1, signal transducer and activator of transcription 1.