Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung's disease.

BACKGROUND AND AIMS: Researchers have not clearly described the clinical and pathogenetic features of hypoganglionosis and adult-onset Hirschsprung's disease, which cause pseudo-obstruction or intractable constipation. We conducted this study to explore these features of hypoganglionosis and adult-onset Hirschsprung's disease in Korean patients.
METHODS: We enrolled 24 patients pathologically confirmed as having hypoganglionosis and 11 as having adult-onset Hirschsprung's disease. We recruited 26 subjects who had undergone operation for nonobstructive colon cancer and 45 healthy volunteers as controls. We described their clinical features, investigated ganglion cells and interstitial cells of Cajal (ICC), and analyzed RET, EDNRB, EDN3, and SOX10 genes.
RESULTS: We classified hypoganglionosis patients into two groups: type I (focal type, n = 13), with focally narrowed transition zone (TZ); and type II (diffuse type, n = 11), without transition zone. Hypoganglionosis patients had significantly fewer ganglion cells than the controls, and those cells were scarcer in the transition zone than in the proximal dilated area (P < 0.05). The ICC numbers in both diseases were significantly lower than in controls; however, they were similar between transition zone and the proximal dilated area in hypoganglionosis. In adult-onset Hirschsprung's disease, two significant intronic RET polymorphic variants, IVS14-24G>A and IVS19+47T>C, were significantly associated with adult-onset Hirschsprung's disease (P = 0.0122 and 0.0295, respectively), but not with hypoganglionosis.
CONCLUSIONS: Hypoganglionosis and adult-onset Hirschsprung's disease have different pathophysiologic characteristics, although their clinical presentations are similar. We suggest that there are two subgroups of hypoganglionosis: those with or without a focally narrowed transition zone with a profoundly diminished number of ganglion cells.