Table 5.

Congenital defects of phagocytic number and/or function

Disease	Affected cells	Functional defects	Genetic defect	Inheritance	Features
Severe congenital neutropenia (Kostmann)	N	–	Elastase 2	AD	Subgroup with myelodysplasia
Cyclic neutropenia	Mainly N	–	Elastase 2	AD	Oscillations of other leucocytes, reticulocytes and platelets
X-linked neutropenia	N + M	–	WASP	XL	–
Leucocyte adhesion defect 1	N + M+ L + NK	Chemotaxis, adherence, endocytosis	CD18 (of LFA-1, Mac 1, p 150,95)	AR	Delayed cord separation, chronic skin ulcers, periodontitis, leucocytosis, defective T + NK cell cytotoxicity
Leucocyte adhesion defect 2	Mainly N + M	Chemotaxis, rolling	GDP-fucose-transporter	AR	Delayed wound healing, chronic skin ulcers, periodontitis, leucocytosis, Bombay blood group, mental retardation
Rac-2 GTPase-defect	N	Chemotaxis, adherence	GTPase Rac2	AD	Delayed wound healing, leucocytosis
Localized juvenile periodontitis	N	Formyl peptide-induced chemotaxis	Formyl peptide receptor	AR	Periodontitis
Specific granule defect	N	Chemotaxis	CCAAT/enhancer binding protein ɛ	AR	N with bi-lobed nuclei
Shwachman–Diamond syndrome	N	Chemotaxis	Unknown	AR	Pancytopenia, pancreatic insufficiency, chondrodysplasia
Chronic granulomatous disease
(a) X-linked CGD	N + M	Killing (faulty production of superoxide metabolites)	gp 91 phox	XL	McLeod phenotype*
(b) Autosomal CGDs	N + M	Killing − as above	p22 phox; p47 phox; p67 phox	AR
Neutrophil G-6 PD defect	N + M	Killing	Glucose-6-P-dehydrogenase	XL	Haemolytic anaemia
Myeloperoxidase deficiency	N	Killing	MPO	AR	This deficiency may be found in normal people
Leucocyte mycobactericidal defects:		Killing – failure of upregulation of interferon production			Susceptibility to mycobacteria and salmonella
(a) IFN-γ receptor defects	M		IFN-γR1; IFN-γR2	AR/AD; AR
(b) STAT-1-defect	M		STAT-1	AD
(c) Interleukin-12-receptor defect	L + NK		IL12Rβ1	AR
(d) Interleukin-12-defect	M		IL12p40	AR

New defects: a new form of leucocyte adhesion defect is due to a mutation in the small GTPase Rac2. There is defective chemotaxis and poor adherence of neutrophils in affected patients who display delayed wound healing.

Another form of LAD has been found in children with localized periodontitis caused by mutations in the formyl peptide receptor.

Another leucocyte mycobactericidal defect has been found in patients with mutations in the STAT1 gene, which encodes the transcription factor that is activated by the interferon-γ receptor.

^*Some patients have deletions in the short arm of the X-chromosome; in these patients additional features, including McLeod phenotype, retinitis pigmentosa and Duchenne muscular dystrophy, may be found.

Abbreviations: As for Table 1; N, neutrophils; M, monocytes/macrophages; L, lymphocytes; NK, natural killer cells; AD, autosomal dominant inheritance.