Transient hypogammaglobulinemia and unclassified hypogammaglobulinemia: Similarities and differences

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin (Ig) levels. Usually, this clinical picture resolves spontaneously by 3 yr of age. However, hypogammaglobulinemia persists until adolescence in some patients. In recent years, those patients have been classified as undefined/unclassified hypogammaglobulinemia (UCH). We aimed to evaluate the clinical and immunologic features of patients with THI and UCH considering age of recovery and to assess relationships between hypogammaglobulinemia, infections, and allergic manifestations. We reviewed the medical records of children followed with a diagnosis of hypogammaglobulinemia from 2001 to 2007. Patients with decreased levels (<2 s.d.) of one or more major Ig isotypes (IgG, IgA, IgM) with normal antibody responses and lymphocyte subpopulations were included (n = 374). Those patients whose Igs normalized during the follow-up period were classified as THI and the others as UCH. The THI group consisted of 71 patients (27 females, 44 males) with a mean recovery age of 68.87 ± 36.5 months. About 95% of patients with THI recovered before 10 yr of age. The UCH group consisted of 303 patients (105 females, 198 males) with a mean age at diagnosis of 52 ± 42 months. The most common presenting manifestations in the THI and UCH groups were upper respiratory tract infections (URTIs), lower respiratory tract infections, and asthma (42%, 50%, and 52% in the THI group vs. 39%, 53%, and 55% in the UCH group, respectively). In the THI group, the prevalence of atopic disease was related to age and found to be increased markedly after 44 months. In all patients, the prevalence of asthma was independently and positively associated with family history of atopy and age, whereas it was negatively associated with recurrent URTIs. Patients with THI and UCH have similar clinical and immunologic features. The normalization of Igs may be delayed in a majority of the patients with hypogammaglobulinemia. This observation may be a contribution to the classical definition and diagnostic criteria for THI. © 2010 John Wiley & Sons A/S.