The outcome of patients with unclassified hypogammaglobulinemia in early childhood.

Symptomatic hypogammaglobulinemia in childhood may be the initial finding of primary immunodeficiency (PID) or may be due to delay in maturation of immunoglobulin synthesis. The aim of this study was to review the clinical and laboratory records of patients with unclassified hypogammaglobulinemia and to evaluate whether these children experience changes in serum immunoglobulin concentrations during long-term followup and have an exact diagnosis in natural course of disease. We reviewed the data of 412 patients who were diagnosed as PID with symptomatic hypogammaglobulinemia. Thirty-seven patients with hypogammaglobulinemia [19 males (51.4%) and 18 females (48.6%), with a followup of 34.1 +/- 22.0 months] who were not classified according to European Society for Immunodeficiencies diagnostic criteria were included in this study. The mean age at the beginning of the symptoms was 21.4 +/- 20.6 months and the mean age at admission was 51.5 +/- 25.8 months. The commonest clinical presentations were recurrent upper (94.6%) and/or lower (40.5%) respiratory infections, urinary infection (27%) and gastroenteritis (10.8%). Percentage of consanguinity was 8%. Of the initial 37 patients, 18 (48.6%) spontaneously corrected their immunoglobulin abnormalities during followup. Clinical symptoms of these patients were also improved. IgG, IgA and IgM levels reached to normal levels at ages 62.5 +/- 21.8, 72.0 +/- 11.2, 55.2 +/- 7.8 months, respectively. In remaining 19 patients with undefined/unclassified hypogammaglobulinemia, three partial IgA deficiency, seven IgG subclass deficiency, two selective IgM deficiency and two common variable immunodeficiency (CVID) were diagnosed by long-term monitoring of immunoglobulin levels. Five (13.5%) of the 37 unclassified patients could not be exactly diagnosed while two of them might have a T-cell defect and three of them still had low IgG and IgA levels but adequate antibody responses against vaccine antigens. In conclusion, it is important to monitor symptomatic patients with hypogammaglobulinemia periodically. Some children may spontaneously correct their immunoglobulin abnormalities not in the first 30 months of age, but during the first decade of life and some of them may have a severe PID like CVID.