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Monogene und syndromale Krankheitsbilder bei morbider Adipositas

Selten aber wichtig

Monogenic and syndromic symptoms of morbid obesity

Rare but important

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Zusammenfassung

Hintergrund

Monogene und syndromale Adipositasformen sind selten und können klinisch variabel auftreten. Eine Differenzialdiagnose ist daher schwierig.

Fragestellung

Es sollten Kriterien für einen klinischen und molekularen Algorithmus zur Differenzialdiagnose von monogener und syndromaler Adipositas entwickelt werden.

Material und Methoden

Verfügbare Publikationen zum klinischen Erscheinungsbild und zu molekularen Defekten von monogenen und syndromalen Adipositasfällen wurden ausgewertet.

Ergebnisse

Eine monogene und syndromale Adipositas kann bei einer frühen Manifestation vor dem 5. Lebensjahr und Body-Mass-Index-Werten über 40 bzw über der 99. Perzentile vorliegen. Syndromale Fälle sind meist durch einen niedrigen IQ-Wert und einen Kleinwuchs charakterisiert. Monogene Störungen treten mit anderen endokrinen Störungen assoziiert auf. Die Bestimmung des Serumleptinwerts weist einen Leptinmangel nach. Für die Behandlung des Leptindefekts steht eine kausale Substitutionstherapie zur Verfügung. Die Sequenzierung des Melanocortin-4-Rezeptor(MC4R)-Gens weist die häufigste monogene Adipositasform nach. Eine Behandlung mit einem Analogon des melanozytenstimulierenden Hormons (MSH) ist für leptinresistente Fälle absehbar. Mit einer frühzeitigen Gabe von Wachstumshormon kann eine Adipositas bei Prader-Willi-Syndrom verhindert werden.

Schlussfolgerung

Aufgrund der teilweise verfügbaren kausalen Therapie sollte eine frühe Diagnose der monogenen und syndromalen Adipositas gestellt werden. Aus den jeweiligen Krankheitssymptomen, dem Serumleptinwert und der MC4R-Sequenzierung, lässt sich ein Diagnosealgorithmus ableiten, der eine Zuordnung der morbiden Adipositasfälle zu den einzelnen Diagnoseentitäten ermöglicht.

Abstract

Background

Monogenic and syndromic obesity are rare diseases with variable manifestation. Therefore diagnosis is difficult and often delayed.

Objectives

The purpose of this work was to develop a clinical diagnostic algorithm for earlier diagnosis.

Material and methods

Available publications for clinical symptoms and molecular defects of monogenic and syndromic obesity cases were evaluated.

Results

Monogenic and syndromic obesity can be expected in cases with early manifestation before the age of 5 years and a BMI above 40 or above the 99th percentile. Syndromic cases are mostly associated with a low IQ and dwarfism. Monogenic cases are associated with additional endocrine defects. Measurement of serum leptin proves the treatable leptin deficiency. Sequencing of the melanocortin-4 receptor gene (MC4R) allows diagnosis of the most frequent monogenic form of obesity. Treatment with a melanocyte-stimulating hormone (MSH) analog can be expected in the future. Early treatment of children with Prader–Willi syndrome can prevent severe obesity.

Conclusion

Because in some cases treatment is available, monogenic and syndromic obesity should be diagnosed early. Based on the disease symptoms, serum leptin, and MC4R sequencing, a diagnostic algorithm is proposed, which can be used to diagnose cases of morbid obesity.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. S. Wiegand und H. Krude geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Sozialpädiatrisches Zentrum (SPZ), Charité-Universitätsmedizin Berlin, Berlin, Deutschland

    S. Wiegand

  2. Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin-Berlin, Augustenburgerplatz 1, 13353, Berlin, Deutschland

    H. Krude

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  1. S. Wiegand
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Wiegand, S., Krude, H. Monogene und syndromale Krankheitsbilder bei morbider Adipositas. Internist 56, 111–120 (2015). https://doi.org/10.1007/s00108-014-3532-8

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  • DOI: https://doi.org/10.1007/s00108-014-3532-8

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