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Hypoganglionose als Ursache chronischer Obstipation

Hypoganglionosis as a cause of chronic constipation

  • Schwerpunkt: Gastrointestinale Motilitätsstörungen
  • Published:
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Zusammenfassung

Die mit einer chronischen therapieresistenten Obstipation verbundene Hypoganglionose macht 3–5% der bioptisch abzuklärenden gastrointestinalen Innervationsstörungen im Kindes- und Erwachsenenalter aus. Sie kann wie der M. Hirschsprung zu einem Megakolon führen und muss als wichtige Differenzialdiagnose berücksichtigt werden. Es lassen sich 3 Hauptformen der Hypoganglionose unterscheiden: Die kongenitale hypoplastische Hypoganglionose tritt vorwiegend beim klassischen M. Hirschsprung proximal des aganglionären Segments auf. Sie zeigt kleine zellarme Ganglien mit großen interganglionären Abständen. Die oligoneuronale dysganglionäre Hypoganglionose manifestiert sich im Kindesalter und ist charakterisiert durch eine zunächst normale Zahl hypoplastischer Nervenzellen normal großer Ganglien des Plexus myentericus. Diese Form der Hypoganglionose kann progressiv verlaufen und in eine atrophische Hypoganglionose münden, die im Erwachsenenalter ein der Hirschsprung-assoziierten hypoplastischen Hypoganglionose ähnliches morphologisches Bild zeigt. Alle Formen äußern sich in einer verminderten Acetylcholinesterase-Aktivität der Nervenfasern der Muscularis propria. Über die Ätiologie der Hypoganglionose ist wenig bekannt: Bei den Hirschsprung assoziierten Formen sind vereinzelt Mutationen im RET- und GDNF-Gen nachgewiesen worden. Im heterozygoten GDNF+/--Tiermodell führt die GDNF-Mutation zur Hypoganglionose, was bei der isolierten Hypoganglionose des Menschen noch zu belegen ist.

Abstract

Hypoganglionosis comprises 3–5% of gastrointestinal innervation defects which are connected to therapy-resistant chronic constipation in children and adults. Similar to Hirschsprung’s disease, hypoganglionosis may be complicated by megacolon formation and must be considered in the differential diagnosis. Three main subtypes may be distinguished: congenital hypoplastic hypoganglionosis occurs predominantly in Hirschsprung’s disease proximal to the aganglionic segment and consists of small paucicellular ganglia with increased interganglionic distances. Oligoneuronal dysganglionic hypoganglionosis manifests in childhood. Initially, myenteric ganglia are of normal size and have normal interganglionic spacing and normal neuronal content. However, nerve cells are hypoplastic and ganglia undergo progressive nerve cell loss. This type of hypoganglionosis may progress into atrophic hypoganglionosis, which shows a morphology similar to hypoplastic hypoganglionosis. All subtypes of hypoganglionosis result in decreased acetylcholinesterase activity in the nerve fiber network of the muscularis propria. The pathogenesis of hypoganglionosis is still poorly understood. In Hirschsprung associated hypoganglionosis, mutations in the RET and GDNF-genes have been found. Despite a heterozygote GDNF+/- animal model for hypoganglionosis, no GDNF mutations have so far been demonstrated in human Hirschsprung independent, isolated hypoganglionosis.

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  1. Institut für Pathologie, Universitätsspital Basel, Schönbeinstraße 40, 4031, Basel, Schweiz

    E. Bruder &  W.A. Meier-Ruge

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  1. E. Bruder
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  2. W.A. Meier-Ruge
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Correspondence to W.A. Meier-Ruge.

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Bruder, E., Meier-Ruge, W. Hypoganglionose als Ursache chronischer Obstipation. Pathologe 28, 131–136 (2007). https://doi.org/10.1007/s00292-007-0892-z

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