Children with Hirschsprung's disease have an abnormal colonic mucus defensive barrier independent of the bowel innervation status.

The mucus gel layer in the colon plays an important role in the defensive mechanisms against pathogenic organisms. Mucin glycoproteins or mucins are the major component of this gel. We studied the mucins in patients who had Hirschsprung's disease (HD) by colonic mucosal organ culture with radioactive mucin precursors [35S]-sulphate and [3H]-glucosamine. The secreted and cellular mucus fractions were collected after 24-hour incubation, and mucins were purified by gel filtration. The ratio of incorporation of the precursors and their turnover were quantified. Purified mucins were tested against wheat germ agglutinin for total mucin turnover. We used nine aganglionic bowel samples, 10 ganglionic bowel samples from HD patients, and 13 age-matched normal controls. There were no significant differences in the three groups in ratio of incorporation. The turnover with both radioactive precursors was reduced in both aganglionic and ganglionic bowel of HD, these differences were significant in [35S]-sulphate incorporation in the cellular fraction, ganglionic bowel being most affected. Total mucin turnover, as assessed by reactivity with wheat germ aggultinin, was reduced in both HD groups, being significant in the cellular fraction, aganglionic bowel being the most affected. These results signify an abnormal mucus defensive barrier in the colon of HD patients, even in the ganglionic bowel, which is thought to be normal and is retained at the definitive pull-through operation. This abnormality may be an etiological factor in the pathogenesis of enterocolitis of HD.