THI is a heterogeneous disorder with several associated comorbidities. The clinical and immunologic features of a cohort of children with THI were examined.

24 patients diagnosed with hypogammaglobulinemia defined by any Ig isotype level <−2SD below mean on two occasions, not having any other immunologic diagnosis were followed prospectively and reviewed. Serial immunologic analyses were collected along with detailed clinical profiles.

The mean at diagnosis of hypogammaglobulinemia was 12 mos (male:female=1.2). 18 patients were followed to resolution with 12/18 normalizing by 24 mos and the remainder by 59 mos. The mean age at resolution was 27 mos. The average z-score for IgG level at presentation was −2.4 with a mean level of 254 mg/dl. 13/24 patients had IgA levels <−2SD, and 5 had IgM levels <−2SD, and 7/23 had elevated IgE levels. 4/14 patients had absolute CD19+ B cells >95% for age and the mean percentage and absolute counts of CD19+ B cells was greater than that expected for age-matched controls (p=0.01). All but 2 patients had evidence of tetanus-specific antibody production at their initial evaluation. 20/24 patients carried at least one atopic diagnosis, and 5/24 had some form of developmental delay. 19/14 patients received prophylactic antibiotics and 5 patients received gammaglobulin therapy due to clinically inadequate response to antibiotics.

THI is a heterogeneous disorder often presenting and resolving well beyond infancy. A notable number of these patients have significant comorbidities. Observed elevation in B-cells may be suggestive of particular immunologic mechanisms resulting in hypogammaglobulinemia.