title: Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung's disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, Seoul 138-736, Korea.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Do
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Myung
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Jun-Won
authors.initials: JW
authors.lastname: Chung
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Byong Duk
authors.initials: BD
authors.lastname: Ye
authors.forename: Jeong-Sik
authors.initials: JS
authors.lastname: Byeon
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003106:Colon / Q000294:innervation*; D005260:Female; D005725:Ganglia, Autonomic / Q000473:pathology*; D005786:Gene Expression Regulation; D006627:Hirschsprung Disease / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009197:Myenteric Plexus / Q000166:cytology; D011110:Polymorphism, Genetic; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human