Table 3.

Other well-defined immunodeficiency syndromes

Designation	Serum Ig and antibodies	Circulating B cells	Circulating T cells	Genetic defect	Inheritance	Associated features
1. Wiskott–Aldrich syndrome	Decreased IgM: antibody to polysaccharides particularly decreased; often increased IgA and IgE	Normal	Progressive decrease	Mutations in WASp gene; cytoskeletal defect affecting haematopoietic stem cell derivatives	XL	Thrombocytopenia; small defective platelets; eczema; lymphomas; autoimmune disease
2. Ataxia-telangiectasia	Often decreased IgA, IgE and IgG subclasses; increased IgM monomers; antibodies variably decreased	Normal	Decreased	Mutation in A-T gene (ATM); disorder of cell cycle check-point pathway leading to chromosomal instability	AR	Ataxia; telangiectasia; increased alpha fetoprotein; lympho-reticular and other malignancies; increased X-ray sensitivity
(a) Ataxia-like syndrome	Often decreased IgA, IgE and IgG subclasses; increased IgM monomers; antibodies variably decreased	Normal	Decreased	Mutation in Mre 11	AR	Moderate ataxia; severely increased radiosensitivity
3. Nijmegen breakage syndrome	Often decreased IgA, IgE and IgG subclasses; increased IgM monomers; antibodies variably decreased	Normal	Decreased	Defect in NBS1 (Nibrin); disorder of cell cycle checkpoint and DNA double- strand break repair	AR	Microcephaly lymphomas; ionizing radiation sensitivity; chromosomal instability
4. DiGeorge anomaly	Normal or decreased	Normal	Decreased or normal	Contiguous gene defect in 90% affecting thymic development	De novo defect or AD	Hypoparathyroidism: conotruncal malformation; abnormal facies; partial monosomy of 22q11-pter or 10p in some patients
5. Imunodeficiency with albinism
(a) Chediak Higashi syndrome	Normal	Normal	Normal	Defect in Lyst	AR	Albinism; acute phase reaction; low NK and CTL activities; giant lysosomes
(b) Griscelli syndrome	Normal	Normal	Normal	Defect in myosin 5a, or RAB27A	AR	Albinism; acute phase reaction; low NK and CTL activities; progressive encephalopathy in severe cases
6. X-linked lympho-proliferative syndrome	Normal or rarely hypogammaglobulinaemia	Normal or reduced	Normal	Defect in SAP/SH2DRA	XL	Clinical and immunological manifestations induced by EBV infection; hepatitis; aplastic anaemia; lymphomas
7. Familial haemaphagocytic lymphohistiocytosis	Normal	Normal	Normal	Mutation in perforin gene	AR	Decreased NK and CTL activities
8. Immune dysregulation, polyendocrinopathy, enteropathy, X–linked syndrome (IPEX)	Normal or increased	Normal	Normal, activated phenotype	Mutation in FOXP3	XL	Severe skin involvement; early onset IDDM
9. Autoimmune polyendocrinopathy and ectodermal dysplasia	Normal	Normal	Normal	Mutation in AIRE	AR	Chronic mucocutaneous candidiasis
10. X-linked immunodeficiency and ectodermal dysplasia	Often low IgG and IgA with normal or high IgM	Normal	Normal	Mutation in NEMO/IKKγ	XL	Conical teeth and sparse hair

New defects: an ataxia telangiectasia-like syndrome is due to mutations in the gene encoding Mre11, an enzyme involved in DNA repair.

Another X-linked immunodeficiency associated with ectodermal dysplasia has been found to be due to a mutation in the scaffolding γ subunit of the NF-κB activator (IKKk/NEMO). These patients have sparse hair, conical malformed teeth and defects in activation of monocytes, NK cells, T cells and B cells.

Abbreviations: As for Table 1; CTL, cytotoxic T lymphocytes; EBV, Epstein Barr Virus; IDDM, insulin-dependent diabetes mellitus.