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Novel Classification and Pathogenetic Analysis of Hypoganglionosis and Adult-Onset Hirschsprung’s Disease

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Abstract

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.

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Acknowledgments

The authors thank Ms. Hyun Suk Song for her assistance with data collection. This work was supported by a grant (2008-0261) from the Asan Institute for Life Sciences and the Korean Society of Neurogastroenterology and Motility (2009).

Conflict of interest

None of the authors has any conflict of interest to declare.

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Authors and Affiliations

  1. 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

    Mi Young Do, Seung-Jae Myung, Byong Duk Ye, Jeong-Sik Byeon, Suk-Kyun Yang & Jin-Ho Kim

  2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

    Hyo-Jin Park

  3. Department of Internal Medicine, Gachon Graduate School of Medicine, Incheon, Korea

    Jun-Won Chung

  4. Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea

    In-Wha Kim, Sun Mi Lee & Jong-Keuk Lee

  5. Colorectal Clinic, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Chang Sik Yu

  6. Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Hye Kyung Lee

  7. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Young Soo Park & Se Jin Jang

  8. Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Hye Jin Kim

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  1. Mi Young Do
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Correspondence to Seung-Jae Myung.

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Do, M.Y., Myung, SJ., Park, HJ. et al. Novel Classification and Pathogenetic Analysis of Hypoganglionosis and Adult-Onset Hirschsprung’s Disease. Dig Dis Sci 56, 1818–1827 (2011). https://doi.org/10.1007/s10620-010-1522-9

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  • DOI: https://doi.org/10.1007/s10620-010-1522-9

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