Journal of Clinical Immunology

, Volume 26, Issue 1, pp 7–11

Infants Presenting with Recurrent Infections and Low Immunoglobulins: Characteristics and Analysis of Normalization

  • M. A. Whelan
  • W. H. Hwan
  • J. Beausoleil
  • W. W. Hauck
  • S. J. Mcgeady


To better characterize infants presenting with diminished immunoglobulin levels and intact antibody formation, we present 49 such infants, correlating presenting characteristics with history and time to immunoglobulin normalization. Term infants with the following characteristics were included: 1) one or more immunoglobulin classes > 2SD below mean, 2) protective antibody titer to tetanus and diphtheria, 3) intact cellular immunity, 4) no features of other syndromes. The children were 69.4% male and had recurrent otitis media (77.6%), wheezing (61.2%), and atopy (26.5%). Diminished IgA (95.9%) was most common, but 65.3% had multiple isotypes diminished. During follow-up, 25/49 (51%) normalized immunoglobulins, of whom 80% were male; only 48% normalized in infancy. Female immunoglobulin normalization was significantly delayed (p < .001). No deaths or serious infections occurred. This phenotype is predominantly seen in male infants with otitis media and wheezing. Female infants have significantly delayed immunoglobulin normalization. Transient hypogammaglobulinemia of infancy can be diagnosed only retrospectively.


Atopy immunoglobulin normalization low immuno-globulins primary immune deficiency transient hypogammaglobulinemia of infancy (THI) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gitlin D, Janeway CA: Agammaglobulinemia, congenital, acquired and transient forms. Prog Hematol 1:318–329, 1956PubMedGoogle Scholar
  2. 2.
    Primary immunodeficiency diseases. Report of a WHO Scientific Group. Clin Exp Immunol 109 Suppl 1:1–28, 1997Google Scholar
  3. 3.
    Notarangelo L, Casanova JL, Fischer A, Puck F, Rosen F, Seger R, et al.: Primary immunodeficiency diseases: An update. J Allergy Clin Immunol 114:677–687, 2004CrossRefPubMedGoogle Scholar
  4. 4.
    McGeady SJ: Transient hypogammaglobulinemia of infancy: Need to reconsider name and definition. J Pediatr 110:47–50, 1987PubMedGoogle Scholar
  5. 5.
    Buckley RH: Immunodeficiency. J Allergy Clin Immunol 72:627–641, 1983CrossRefPubMedGoogle Scholar
  6. 6.
    Dressler F, Peter HH, Muller W, Rieger CH: Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition. Acta Paediatr Scand 78:767–774, 1989PubMedGoogle Scholar
  7. 7.
    Tiller TL Jr, Buckley RH: Transient hypogammaglobulinemia of infancy: Review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up. J Pediatr 92:347–353, 1978PubMedGoogle Scholar
  8. 8.
    Siegel RL, Issekutz T, Schwaber J, Rosen FS, Geha RS: Deficiency of T helper cells in transient hypogammaglobulinemia of infancy. N Engl J Med 305:1307–1313, 1981PubMedGoogle Scholar
  9. 9.
    Cano F, Mayo DR, Ballow M: Absent specific viral antibodies in patients with transient hypogammaglobulinemia of infancy. J Allergy Clin Immunol 85:510–513, 1990CrossRefPubMedGoogle Scholar
  10. 10.
    Walker AM, Kemp AS, Hill DJ, Shelton MJ: Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities. Arch Dis Child 70:183–186, 1994PubMedGoogle Scholar
  11. 11.
    Kowalczyk D, Mytar B, Zembala M: Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol 100:556–562, 1997CrossRefPubMedGoogle Scholar
  12. 12.
    Dalal I, Reid B, Nisbet-Brown E, Roifman CM: The outcome of patients with hypogammaglobulinemia in infancy and early childhood. J Pediatr 133:144–146, 1998PubMedGoogle Scholar
  13. 13.
    Dogu F, Ikinciogullari A, Babacan E: Transient hypogammaglobulinemia of infancy and early childhood: Outcome of 30 cases. Turk J Pediatr 46:120–124, 2004PubMedGoogle Scholar
  14. 14.
    Kilic SS, Tezcan I, Sanal O, Metin A, Ersoy F: Transient hypogammaglobulinemia of infancy: Clinical and immunologic features of 40 new cases. Pediatr Int 42:647–650, 2000CrossRefPubMedGoogle Scholar
  15. 15.
    Soothill JF: Immunoglobulins in first-degree relatives of patients with hypogammaglobulinaemia. Transient hypogammaglobulinaemia: A possible manifestation of heterozygocity. Lancet 1:1001–1003, 1968PubMedGoogle Scholar
  16. 16.
    Turkeltaub PC, Gergen PJ: Prevalence of upper and lower respiratory conditions in the US population by social and environmental factors: Data from the second National Health and Nutrition Examination Survey, 1976–1980 (NHANES II). Ann Allergy 67:147–154, 1991PubMedGoogle Scholar
  17. 17.
    Roifmman CM: Transient hypogammaglobulinemia of infancy. In Immunologic Disorders in Infants and Children, 5th ed., ER Stiehm, HD Ochs, JA Winkellstein (eds). Philadelphia, Elsevier Saunders, 2004, pp 341–393Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • M. A. Whelan
    • 1
  • W. H. Hwan
    • 1
  • J. Beausoleil
    • 2
  • W. W. Hauck
    • 3
  • S. J. Mcgeady
    • 4
    • 5
  1. 1.Division of Allergy & ImmunologyThomas Jefferson UniversityPhiladelphia
  2. 2.Division of Allergy & ImmunologyChildren's Hospital of PennsylvaniaPhiladelphia
  3. 3.Biostatistics Section Division of PharmacologyThomas Jefferson UniversityPhiladelphia
  4. 4.Division of Allergy & ImmunologyAlfred I. duPont Hospital for Children, Nemours Children's ClinicWilmington
  5. 5.Division of Allergy & ImmunologyAlfred I. duPont Hospital for ChildrenWilmington

Personalised recommendations