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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 hypogammaglobulinemia of infancy (THI) was classically described as an accentuation and prolongation of the "physiologic" immunoglobulin nadir that is normally observed during the first three to six months of life (figure 1) [1,2]. However, there remains no full agreement among immunologists regarding the definition of THI due to the absence of specific markers or a genetic signature. While some use sweeping inclusion criteria such as a reduction in any immunoglobulin (immunoglobulin G [IgG], immunoglobulin A [IgA], immunoglobulin M [IgM]), beyond the physiologic nadir [2-7], most agree that low IgG is essential for considering the diagnosis [8-12].

The definition proposed by the International Union of Immunological Societies (IUIS) committee [13] calling for obligatory low IgG and IgA in THI poses multiple challenges. It excludes all cases of isolated, transient low IgG (4 to 45 percent of cases of classically defined THI [3,8,10,14]) and also includes other entities such as hyper-IgM syndrome and common variable immunodeficiency (CVID) [15]. The European Society for Immunodeficiencies (ESID) has proposed the term "unclassified hypogammaglobulinemia" for children in the first three years of life with low IgG levels, reserving THI for those children that recover by age four years [16].

The authors of this topic use a more conservative and balanced definition, which, on one hand, is flexible enough to include most cases historically considered to have THI but sufficiently restrictive to prevent confusion with other possible conditions. It encompasses low serum IgG levels in the presence or absence of low IgA or IgM (consistent with the ESID criteria) and normalization of IgG levels, as well as specific antibodies, over time. Hypogammaglobulinemia associated with a reduction in circulating B cells, abnormal cellular immunity, and syndromic features is excluded from the definition of THI.

It is important to recognize that the diagnosis of THI is made retrospectively. It is one of several possible diagnoses considered in the heterogeneous population of young children presenting with recurrent infections and low immunoglobulins.

This topic reviews the clinical features, diagnosis, and management of THI. Other humoral immune defects are reviewed in greater detail separately. (See "Primary humoral immunodeficiencies: An overview".)


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Literature review current through: Dec 2016. | This topic last updated: Mon Oct 24 00:00:00 GMT+00:00 2016.
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