Table I.

Combined T and B cell immunodeficiencies

Disease	Circulating T cells	Circulating B cells	Serum Ig	Associated Features	Inheritance	Genetic defects/presumed pathogenesis
1. T−B+ SCID*
(a) γc deficiency	Markedly decreased	Normal or increased	Decreased	Markedly decreased NK cells	XL	Defect in γ chain of receptors for IL-2, -4, -7, -9, -15, -21
(b) JAK3 deficiency	Markedly decreased	Normal or increased	Decreased	Markedly decreased NK cells	AR	Defect in JAK3 signaling kinase
(c) IL7Rα deficiency	Markedly decreased	Normal or increased	Decreased	Normal NK cells	AR	Defect in IL-7 receptor α chain
(d) CD45 deficiency	Markedly decreased	Normal	Decreased	Normal γ/δ T cells	AR	Defect in CD45
(e) CD3δ/CD3ε /CD3 ζ deficiency	Markedly Decreased	Normal	Decreased	Normal NK cells	AR	Defect in CD3δ CD3ε or CD3ζ chains of T cell antigen receptor
2. T−B−SCID*
(a) RAG 1/2 deficiency	Markedly decreased	Markedly decreased	Decreased	Defective VDJ recombination	AR	Complete defect of recombinase activating gene (RAG) 1 or 2
(b) DCLRE1C (Artemis) deficiency	Markedly decreased	Markedly decreased	Decreased	Defective VDJ recombination, radiation sensitivity	AR	Defect in Artemis DNA recombinase-repair protein
(c) Adenosine deaminase deficiency (ADA)	Absent from birth (null mutations) or progressive decrease	Absent from birth or progressive decrease	Progressive decrease	Costochondral junction flaring	AR	Absent ADA, elevated lymphotoxic metabolites (dATP, S-adenosyl homocysteine)
(d) Reticular dysgenesis	Markedly decreased	Decreased or normal	Decreased	Granulocytopenia, thrombocytopenia (deafness)	AR	Defective maturation of T, B and myeloid cells (stem cell defect)
3. Omenn syndrome	Present; restricted heterogeneity	Normal or decreased	Decreased, except increased IgE	Erythroderma, eosinophilia, adenopathy, hepatosplenomegaly	AR	Missense mutations allowoing residual activity, usually in RAG1 or 2 genes but also in Artemis , IL-7Rα and RMRP genes
4. DNA ligase IV	Decreased	Decreased	Decreased	Microcephaly, facial dystrophy, radiation sensitivity	AR	DNA ligase IV defect, impaired nonhomologous end joining (NHEJ)
5. Cernunnos/XLF deficiency	Decreased	Decreased	Decreased	Microcephaly, in utero growth retardation, radiation sensitivity	AR	Cernunnos defect, impaired NHEJ)
6. CD40 ligand deficiency	Normal	IgM and IgD B memory cells present, but others absent	IgM increased or normal, other isotypes decreased	Neutropenia, thrombocytopenia; hemolytic anemia, (biliary tract and liver disease, opportunistic infections)	XL	Defects in CD40 ligand (CD40L), defective B and dendritic cell signaling
7. CD40 deficiency	Normal	IgM and IgD B cells present, other isotypes absent	IgM increased or normal, other isotypes decreased	Neutropenia, gastrointestinal and liver disease, opportunistic infections	AR	Defects in CD40, defective B and dendritic cell signaling
8. Purine nucleoside phosphorylase deficiency(PNP)	Progressive decrease	Normal	Normal or decreased	Autoimmune haemolytic anaemia, neurological impairment	AR	Absent PNP, T-cell and neurologic defects from elevated toxic metabolites (e.g. dGTP)
9. CD3γ deficiency	Normal (reduced TCR expression)	Normal	Normal		AR	Defect in CD3 γ
10. CD8 deficiency	Absent CD8, normal CD4 cells	Normal	Normal		AR	Defects of CD8 α chain
11. ZAP-70 deficiency	Decreased CD8, normal CD4 cells	Normal	Normal		AR	Defects in ZAP-70 signaling kinase
12. Ca++ channel deficiency	Normal counts, defective TCR mediated activation	Normal counts	Normal	Autoimmunity , anhydrotic ectodermic dysplasia, non progressive myopathy	AR	Defect in Orai-1, a Ca++ channel component
13. MHC class I deficiency	Decreased CD8, normal CD4	Normal	Normal	Vasculitis	AR	Mutations in TAP1, TAP2 or TAPBP (tapasin) genes giving MHC class I deficiency
14. MHC class II deficiency	Normal number, decreased CD4 cells	Normal	Normal or decreased		AR	Mutation in transcription factors for MHC class II proteins (C2TA, RFX5, RFXAP, RFXANK genes)
15. Winged helix deficiency (Nude)	Markedly decreased	Normal	Decreased	Alopecia, abnormal thymic epithelium (resembles nude mouse)	AR	Defects in forkhead box N1 transcription factor encoded by FOXN1, the gene mutated in nude mice
16. CD25 deficiency	Normal to modestly decreased	Normal	Normal	Lymphoproliferation (lymphadenopathy, hepatosplenomegaly), autoimmunity (may resemble IPEX syndrome), impaired T-cell proliferation	AR	Defects in IL-2R α chain
17. STAT5b deficiency	Modestly decreased	Normal	Normal	Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstital pneumonitis	AR	Defects of STAT5B gene, impaired development and function of γδT cells, Treg and NK cells, impaired T-cell proliferation

Abbreviations: SCID, severe combined immune deficiencies; XL, X-linked inheritance; AR, autosomal recessive inheritance; NK, natural killer cells.

^*Atypical cases of SCID may present with T cells because of hypomorphic mutations or somatic mutations in T cell precursors.