High incidence of hypogammaglobulinemia in infants with diarrhea

Examination of 136 children who were referred to the Pediatric Gastroenterology Clinic at Yale-New Haven Hospital for chronic or severe diarrhea between 1977 and 1981 revealed that 31 patients (22.8%) had serum immunoglobulin levels below the 5th percentile for age. Twenty-four of these 31 patients (77.4%) had normal or near normal serum immunoglobulin levels by their third birthday and most could therefore be classified under the heading "transient hypogammaglobulinemia of infancy," an unexpected finding, as this condition has previously been thought to be rare; only 27 patients with this disorder were reported prior to 1978. While the basic cause of the defect is unknown, it has been linked to a slower than normal maturation of the neonate's ability to secrete immunoglobulins. Comparison of our patients with hypogammaglobulinemia and those with chronic diarrhea but normal immunoglobulins revealed that the former group are younger at presentation (mean, 8.2 months) and at the onset of their diarrhea (3.1 months); the figures for patients without hypogammaglobulinemia were 18.2 and 8.2 months, respectively. Males and females were equally affected, and the diarrhea, which was responsive to a hypoallergenic diet, resolved by 3 years of age as did the hypogammaglobulinemia in nearly all cases. While the etiology of the diarrhea remains obscure, significant problems outside the gastrointestinal tract did not occur. Circumstantial evidence suggests that the most likely cause for the failure of production of IgG, and to a lesser extent IgA antibody, in infants seen with diarrhea may result from a failure of maturation of T cell helper systems rather than any intrinsic defect in the B cell system itself.