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Transient hypogammaglobulinemia of infancy

Ilan Dalal, MD
Chaim M Roifman, MD, FRCPC, FCACB
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS


Transient form of hypogammaglobulinemia of infancy (THI) has been classically defined as an accentuation and prolongation of the "physiologic" hypogammaglobulinemia of infancy, which is normally observed during the first three to six months of life (figure 1). Despite this discovery decades ago [1] and the significant progress in understanding the pathogenesis of other forms of humoral immunodeficiency, very little is known about THI.

This topic review summarizes the characteristics of THI, including definition, possible etiology(ies), clinical manifestations, treatment, and prognosis. The development of the immune system and neonatal immunity, including antibody levels and function, are discussed in detail separately. An overview of primary humoral deficiencies is also presented separately. (See "Immunity of the newborn" and "The development of immune cells in the fetus and neonate" and "Primary humoral immunodeficiencies: An overview".)


Data from cohorts published in 2009 and 2010 demonstrate a disproportionate number of male infants (up to 70 percent) [2-4]. This suggests that transient hypogammaglobulinemia of infancy (THI) is more common in males or that the normal values may vary by both age and sex.


The cause(s) of transient form of hypogammaglobulinemia of infancy (THI) remains unknown despite a large body of research suggesting numerous pathogenic mechanisms that have mostly been rejected [5-15]. It is possible that patients with THI represent the low extreme variant of the normal age-matched controls, rather than a true abnormality of the immune system if the diagnosis is based on immunoglobulin G (IgG) levels of 2 standard deviations (SD; the 95th percentile) below the mean for age-matched controls [16].


Most patients suspected of having transient form of hypogammaglobulinemia of infancy (THI) present with a history of recurrent respiratory infections with or without otitis media and pneumonias. Occasionally, some can present with invasive infections such as cellulitis, bacteremia, and even meningitis. Occasionally, asymptomatic patients are identified, usually because they are screened due to a family history of immunodeficiency.


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Literature review current through: Oct 2015. | This topic last updated: Nov 18, 2015.
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