Transient hypogammaglobulinemia of infancy

Abstract

Transient hypogammaglobulinemia of infancy (THI) is a primary immunodeficiency caused by a transitory drop of the levels of immunoglobulin G (IgG) in an infant beginning between 5 and 24 months of age. Levels typically return to reference range at ages 2 to 6 years. IgG is produced at low levels by the fetus, and it is the only immunoglobulin to cross the placenta. At birth, an infant's IgG level is equivalent to that of its mother. Shortly after birth, infants begin to produce their own IgG, and levels gradually increase to their expected value around 6 months of age. This process overlaps with the declining maternal IgG levels. Physiologic hypogammaglobulinemia is expected and occurs between 3 to 6 months when maternal levels are low, and infant production is low. This physiologic response is typically not clinically significant. In cases of THI, the IgG levels remain significantly lower (two standard deviations) in infants after 6 months of age. Clinically, THI may be characterized by recurrent infections, although some patients remain asymptomatic. The presence of adequate or mildly low serum levels of IgA and IgM levels may also occur. This combination rules out a diagnosis of X-linked agammaglobulinemia. However, other immunodeficiencies such as common variable immunodeficiency are not completely excludable until the transient period is over, and IgG levels return to normal. Diagnosis is usually confirmed retrospectively. Males are more affected than females by a ratio of 2 to 1. The cause and frequency of THI are unknown. Treatment with antibiotics and replacement immunoglobulin therapy is of foremost importance in the management of symptomatic infants.