Genetische Diarrhö bei Strukturschädigung der Darmmukosa

Zusammenfassung

Genetische Diarrhöen als Folge von strukturellen Defekten der Darmmukosa können primärer Natur sein (kongenitale Mikrovillusatrophie) odersekundär auf dem Boden anderer genetischer Erkrankungen (Infektion bei hereditären Immundefekten) entstehen. Klinisch resultiert meist eine Mischform von osmotischer und sekretorischer Diarrhö. Die Abklärung genetischer Mukosastrukturdefektdiarrhöen beruht neben einer genauen Familien- und Ernährungsanamnese auf biochemischer, immunologischer, mikrobiologischer Blut- und Stuhldiagnostik. Um die Art der jeweiligen Strukturdefekte aufklären zu können, sind neben konventionellen lichtmikroskopischen Verfahren auch Immunhistochemie und -fluoreszenz, in situ-Hybridiserung und elektronenmikroskopische Verfahren an Darmschleimhautbiopsaten erforderlich. Immer öfter können die zugrunde liegenden Erkrankungen auch durch molekulargenetische Untersuchungen identifiziert werden. Therapeutisch stellen hereditäre intestinale Mukosastrukturdefekterkrankungen im Gegensatz zu primären funktionellen Störungen des Darmepithels häufig ein großes Problem dar: In vielen Fällen ist, bei mangelndem Ansprechen auf Medikamente und enterale Ernährungstherapie, eine langzeitparenterale Ernährung erforderlich; in ausgewählten Situationen bietet sich die Option einer Darmtransplantation an.

Summary

Genetic diarrhoeas due to structural defects of the intestinal mucosa can be of primary nature (congenital microvillus atrophy) or emerge as a secondary pathology on the ground of a different genetic disease (infection in hereditary immunodeficiencies). Clinically, in most cases, the consequence is a mixed picture of osmotic and secretory diarrhoea. The evaluation of genetic diarrhoeas due to structural mucosal defects is based on a concise history of familial diseases and diet as well as biochemical, immunological and microbiological investigations of blood and feces. To be able to define the nature of the targeted structural defect it will be necessary—besides using conventional histological methods -to apply also more sophisticated procedures, such as detection of aberrant structural proteins or DNA by immunohistochemistry, immunofluorescence, in situ hybridization, electron microscopy of intestinal biopsies. Increasingly often the underlying disease can be identified using molecular genetic analyses. As for treatment, diseases based on hereditary mucosal structural defects – contrary to most primary functional disorders of the gut epithelium – pose a major problem: in many cases with unsatisfactory response to drugs and nutritional therapy long term parenteral nutrition will be unavoidable, in selected patients intestinal transplantation may be an option.

Schlüsselwörter

Genetische Diarrhö - Mukosastrukturdefekte - Therapieprobleme

Keywords

Genetic diarrhoea - mucosal structural defects - treatment problems

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