The Four Most Common Pediatric Immunodeficiencies

  • Richard E. Stiehm
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)


Other than the physiologic hypogammaglobulinemia of infancy, 80% of the confirmed immunodeficiencies consist of four syndromes: transient hypogammaglobulinemia of infancy (THI), IgG subclass deficiency, partial antibody deficiency with impaired polysaccharide responsiveness (IPR), and selective IgA deficiency IgAD. None are life threatening, all can be readily managed, and many recover spontaneously. An exact incidence of these disorders is not known. A summary of immunodeficiency registries in four countries listed IgAD in 27.5% of the patients, IgG subclass deficiency in 4.8%, and THI in 2.3%. The 1999 US survey of primary immunodeficiencies conducted by the Immune Deficiency Foundation found that 17.5% of these patients had IgAD and 24% had IgG subclass deficiency, while THI and IPR were not listed. The Jeffrey Modell Foundation (2005) survey of their global centers in 2004 reported IgAD in 15.5%, subclass deficiencies in 8%, and THI in 2% of their patients.


Primary Immunodeficiency Common Variable Immunodeficiency Antibody Deficiency Pneumococcal Polysaccharide Vaccine Subclass Deficiency 
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  1. al-Attas, R.A. and Rahi, A.H. (1998) Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia. J. Clin. Immunol. 18, 368–371.CrossRefPubMedGoogle Scholar
  2. Ambrosino, D.M., Siber, G.R., Chilmonczyk, B.A., Jernberg, J.B. and Finberg, R.W. (1987) An immunodeficiency characterized by impaired antibody responses to polysaccharides. N. Engl. J. Med. 316, 790–793.CrossRefPubMedGoogle Scholar
  3. Blecher, T.E., Soothill, J.F., Voyce, M.A. and Walker, W.H. (1968) Antibody deficiency syndrome: a case with normal immunoglobulin levels. Clin. Exp. Immunol. 3, 47–56.PubMedGoogle Scholar
  4. Blum, P.M., Hong, R. and Stiehm, E.R. (1982) Spontaneous recovery of selective IgA deficiency. Additional case reports and a review. Clin. Pediatr. 21, 77–80.Google Scholar
  5. Buckley, R.H. (2002) Immunoglobulin G subclass deficiency: fact or fancy? Curr. Allergy Asthma Rep. 2, 356–360.CrossRefGoogle Scholar
  6. Castigli, E., Wilson, S.A., Garibyan, L., Rachid, R., Bonilla, F., Schneider, L. and Geha, R.S. (2005) TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat. Genet. 37, 829–834.CrossRefPubMedGoogle Scholar
  7. Cunningham-Rundles, S. (2004) The effect of aging on mucosal host defense. J. Nutr. Health Aging 8, 20–25.PubMedGoogle Scholar
  8. Dalal, I. and Roifman, C.H. (2006). Transient hypogammaglobulinemia of infancy, UpToDate. Available at
  9. Fudenberg, H.H. and Fudenberg, B.R. (1964) Antibody to hereditary human gamma-globulin (Gm) factor resulting from maternal-fetal incompatibility. Science 145, 170–171.CrossRefPubMedGoogle Scholar
  10. Gitlin, D. and Janeway, C.A. (1956) Agammaglobulinemia, congenital, acquired and transient forms. Prog. Hematol. 1, 318–329.PubMedGoogle Scholar
  11. Granoff, D.M., Shackelford, P.G., Pandey, J.P. and Boies, E.G. (1986a) Antibody responses to Haemophilus influenzae type b polysaccharide vaccine in relation to Km(1) and G2m(23) immunoglobulin allotypes. J. Infect. Dis. 154, 257–264.PubMedGoogle Scholar
  12. Granoff, D.M., Shackelford, P.G., Suarez, B.K., Nahm, M.H., Cates, K.L., Murphy, T.V., Karasic, R., Osterholm, M.T., Pandey, J.P. and Daum, R.S. (1986b) Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine. N. Engl. J. Med. 315, 1584–1590.CrossRefPubMedGoogle Scholar
  13. Herrod, H.G. (1993) Management of the patient with IgG subclass deficiency and/or selective antibody deficiency. Ann. Allergy 70, 3–8.PubMedGoogle Scholar
  14. Hostoffer, R. (2006). IgA deficiency, UpToDate. Available at
  15. Kalfa, V.C., Roberts, R.L. and Stiehm, E.R. (2003) The syndrome of chronic mucocutaneous candidiasis with selective antibody deficiency. Ann. Allergy Asthma Immunol. 90, 259–264.CrossRefPubMedGoogle Scholar
  16. Kanoh, T., Mizumoto, T., Yasuda, N., Koya, M., Ohno, Y., Uchino, H., Yoshimura, K., Ohkubo, Y. and Yamaguchi, H. (1986) Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang. 50, 81–86.CrossRefPubMedGoogle Scholar
  17. Koistinen, J. (1976) Familial clustering of selective IgA deficiency. Vox. Sang 30, 181–190.CrossRefPubMedGoogle Scholar
  18. Kowalczyk, D., Mytar, B. and Zembala, M. (1997) Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J. Allergy Clin. Immunol. 100, 556–562.CrossRefPubMedGoogle Scholar
  19. Lakhanpal, S., O’Duffy, J.D., Homburger, H.A. and Moore, S.B. (1988) Evidence for linkage of IgA deficiency with the major histocompatibility complex. Mayo Clin. Proc. 63, 461–465.PubMedGoogle Scholar
  20. Lefranc, G., Chaabani, H., Van Loghem, E., Lefranc, M.P., De Lange, G. and Helal, A.N. (1983) Simultaneous absence of the human IgG1, IgG2, IgG4 and IgA1 subclasses: immunological and immunogenetical considerations. Eur. J. Immunol. 13, 240–244.CrossRefPubMedGoogle Scholar
  21. Lemmon, J.K. and Knutsen, A.P. (2006). Clinical manifestations, diagnosis and treatment of IgG subclass deficiency, UpToDate. Available at
  22. Migone, N., Oliviero, S., de Lange, G., Delacroix, D.L., Boschis, D., Altruda, F., Silengo, L., DeMarchi, M. and Carbonara, A.O. (1984) Multiple gene deletions within the human immunoglobulin heavy-chain cluster. Proc. Natl. Acad. Sci. U.S.A. 81, 5811–5815.CrossRefPubMedGoogle Scholar
  23. Nathenson, G. (1971) Development of Gm antibodies following injection of anti-Rh gamma globulin. Transfusion 11, 302–306.CrossRefPubMedGoogle Scholar
  24. Oxelius, V.A., Laurell, A.B., Lindquist, B., Golebiowska, H., Axelsson, U., Bjorkander, J. and Hanson, L.A. (1981) IgG subclasses in selective IgA deficiency: importance of IgG2-IgA deficiency. N. Engl. J. Med. 304, 1476–1477.Google Scholar
  25. Rockey, J.H., Hanson, L.A., Heremans, J.F. and Kunkel, H.G. (1964) Beta-2a Aglobulinemia in two healthy men. J. Lab. Clin. Med. 63, 205–212.PubMedGoogle Scholar
  26. Roifman, C.M. (2004). Immunodeficiency disorders: general considerations. In: E.R. Stiehm, H.D. Ochs and J.A. Winkelstein (Eds),Immunologic Disorders in Infants and Children. Philadelphia, Elsevier: 391–393.Google Scholar
  27. Saxon, A., Kobayashi, R.H., Stevens, R.H., Singer, A.D., Stiehm, E.R. and Siegel, S.C. (1980) In vitro analysis of humoral immunity in antibody deficiency with normal immunoglobulins. Clin. Immunol. Immunopathol. 17, 235–244.CrossRefPubMedGoogle Scholar
  28. Schur, P.H., Borel, H., Gelfand, E.W., Alper, C.A. and Rosen, F.S. (1970) Selective gamma-g globulin deficiencies in patients with recurrent pyogenic infections. N. Engl. J. Med. 283, 631–634.CrossRefPubMedGoogle Scholar
  29. Siegel, R.L., Issekutz, T., Schwaber, J., Rosen, F.S. and Geha, R.S. (1981) Deficiency of T helper cells in transient hypogammaglobulinemia of infancy. N. Engl. J. Med. 305, 1307–1313.CrossRefPubMedGoogle Scholar
  30. Sorensen, R.U. and Paris, K. (2006). Selective antibody deficiency with normal immunoglobulins (polysaccharide non-responses), UpToDate. Available at
  31. Stiehm, E.R., Ochs, H.D. and Winkelstein, J.A. (2004a). IgG subclass deficiencies. In: E.R. Stiehm, H.D. Ochs and J.A. Winkelstein (Eds), Immunologic Disorders in Infants and Children. Philadelphia, Elsevier: 393–398.Google Scholar
  32. Stiehm, E.R., Ochs, H.D. and Winkelstein, J.A. (Eds)(2004b). Immunodeficiency disorders: general considerations. In Immunologic Disorders in Infants and Children. Philadelphia, Elsevier: 289–355.Google Scholar
  33. Stiehm, E.R., Ochs, H.D. and Winkelstein, J.A. (Eds)(2004). Impaired polysacchride responsiveness (selective antibody deficiency). In Immunologic Disorders in Infants and Children. Philadelphia, Elsevier: 398–401.Google Scholar
  34. West, C.D., Hong, R. and Holland, N.H. (1962) Immunoglobulin levels from the newborn period to adulthood and in immunoglobulin deficiency states. J. Clin. Invest. 41, 2054–2064.CrossRefPubMedGoogle Scholar
  35. Whelan, M.A., Hwan, W.H., Beausoleil, J., Hauck, W.W. and McGeady, S.J. (2006) Infants presenting with recurrent infections and low immunoglobulins: characteristics and analysis of normalization. J. Clin. Immunol. 26, 7–11.CrossRefPubMedGoogle Scholar
  36. Wood, P.M., Mayne, A., Joyce, H., Smith, C.I., Granoff, D.M. and Kumararatne, D.S. (2001) A mutation in Bruton’s tyrosine kinase as a cause of selective anti-polysaccharide antibody deficiency. J. Pediatr. 139, 148–151.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Mattel Children’s Hospital and David Geffen School on MedicineUCLALos AngelesUSA

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