Table III.

Other well-defined immunodeficiency syndromes.

Disease	Circulating T cells	Circulating B cells	Serum Ig	Associated features	Inheritance	Genetic defects/Presumed Pathogenesis
1. Wiskott-Aldrich syndrome (WAS)	Progressive decrease	Normal	Decreased IgM: antibody to polysaccharides particularly decreased; often increased IgA and IgE	Thrombocytopenia with small platelets; eczema; lymphomas; autoimmune disease; IgA nephropathy; bacterial and viral infections. XL thrombocytopenia is a mild form of WAS, and XL neutropenia is caused by missense mutations in the GTPase binding domain of WASP	XL	Mutations in WASP; cytoskeletal defect affecting haematopoietic stem cell derivatives
2. DNA repair defects (other than those in Table 1)
(a) Ataxia-telangiectasia	Progressive decrease	Normal	Often decreased IgA, IgE and IgG subclasses; increased IgM monomers; antibodies variably decreased	Ataxia; telangiectasia; increased alpha fetoprotein; lympho-reticular and other malignancies; increased X-ray sensitivity; chromosomal instability	AR	Mutation in ATM; disorder of cell cycle check-point and of DNA double- strand break repair
(b) Ataxia- telangiectasia-like disease (ATLD)	Progressive decrease	Normal	Often decreased IgA, IgE and IgG subclasses; increased IgM monomers; antibodies variably decreased	Moderate ataxia; severely increased radiosensitivity	AR	Hypomorphic mutation in MRE11; disorder of cell cycle checkpoint and of DNA double- strand break repair
(c) Nijmegen breakage syndrome	Progressive decrease	Normal	Often decreased IgA, IgE and IgG subclasses; increased IgM monomers; antibodies variably decreased	Microcephaly; bird-like face; lymphomas; ionizing radiation sensitivity; chromosomal instability	AR	Hypomorphic mutation in NBS1 (Nibrin); disorder of cell cycle checkpoint and of DNA double- strand break repair
(d) Bloom Syndrome	Normal	Normal	Reduced	Chromosomal instability; marrow failure; leukemia; lymphoma; short stature; bird like face; sensitivity to the sun telangiectasias	AR	Mutation in BLM, a RecQ-like helicase
3. Thymic defects
DiGeorge anomaly	Decreased or Normal; often progressive normalization	Normal	Normal or decreased	Hypoparathyroidism; conotruncal heart defects; abnormal facies; interstitial deletion of 22q11-pter (or 10p) in some patients	De novo defect or AD	Contiguous gene defect in 90% affecting thymic development; mutation in transcription factorTBX1
4. Immuno-osseous dysplasias
(a) Cartilage hair hypoplasia	Decreased or Normal*	Normal	Normal or reduced. Antibodies variably decreased	Short-limbed dwarfism with metaphyseal dysostosis; sparse hair; anemia; neutropenia; susceptibility to lymphoma and other cancers; impaired spermatogenesis; neuronal dysplasia of the intestine	AR	Mutation in RMRP (RNase MRP RNA)
(b) Schimke syndrome	Decreased	Normal	Normal	Short stature; spondiloepiphyseal dysplasia; intrauterine growth retardation; nephropathy	AR	Mutation in SMARCAL1
5. Hyper-IgE syndromes
(a) Job Syndrome (autosomal dominant HIES)	Normal	Normal	Elevated IgE	Recurrent skin boils and pneumonia often due to Staphylococcus aureus; pneumoatoceles; eczema, nail candidiasis; distinctive facial features (thickened skin, broad nasal tip); failure/delay of shedding primary teeth; hyperextensible joints	AD , many de novo mutations	Mutation in STAT 3
(b) Autosomal recessive HIES with mycobacterial And viral infections	Normal	Normal	Elevated IgE	Susceptibility to intracellular bacteria (Mycobacteria, Salmonella), fungi and viruses; eczema. No skeletal or connective tissue abnormalities	AR	Mutation in TYK2,
				i) CNS hemorrhage, fungal, and viral infections		Unknown
(c) Autosomal recessive HIES with viral infections and CNS vasculitis/hemorrhage	Normal	Normal	Elevated IgE	Susceptibility to bacterial, viral and fungal infections; eczema; vasculitis; CNS hemorrhage. No skeletal or connective tissue abnormalities	AR	Unknown
6. Chronic mucocutaneous candidiasis	Normal	Normal	Normal	Chronic mucocutaneous candidiasis; impaired delayed-type hypersensitivity to candida antigens; autoimmunity; no ectodermal dysplasia	AD, AR, sporadic	Unknown
7. Hepatic venoocculusive disease with immunodeficiency (VODI)	Normal (Decreased memory T cells)	Normal (Decreased memory B cells)	Decreased IgG, IgA, IgM	Hepatic veno-occulusive disease; Pneumocystis jiroveci pneumonia; thrombocytopenia, hepatosplenomegaly	AR	Mutation in SP110
8. Hoyeraal-Hreidarsson syndrome	Progressive decrease	Progressive decrease	Variable	Intrauterine growth retardation, microcephaly, digestive tract involvement, pancytopenia, reduced number and function of NK cells	XL	Mutation in Dyskerin

^*Patients with cartilage-hair hypoplasia can present also with typical SCID or with Omenn syndrome

HIES: hyper-IgE syndrome; CNS: central nervous system