Monogene Formen der Adipositas beim Menschen

Zusammenfassung

Es gilt Patienten mit sehr seltenen Formen der monogenen Adipositas zu identifizieren um ihnen eine optimierte oder bestenfalls sogar kausale Therapie anbieten zu können. Hinweise für eine monogene Adipositasform sind insbesondere extreme Adipositas, frühkindlicher Beginn der Adipositas, sowie auffälliges Essverhalten mit Hyperphagie, ausgeprägtem nahrungssuchendem Verhalten und fehlendem Sättigungsgefühl. Mutationen in Genen, die den Leptin-Melanocortin-Signalweg betreffen, verursachen die wichtigsten Formen der monogenen Adipositas. Dabei sind Mutationen im Melanocortin-4-Rezeptor Gen (MC4R) am häufigsten. Zu einer ausgeprägten frühkindlichen Adipositas kommt es bei autosomal rezessiv vererbten Mutationen in den Genen für Leptin (LEP), Leptinrezeptor (LEPR), Proopiomelanocortin (POMC) und Prohormonkonvertase 1/3 (PCSK1). Eine kausale Therapie ist bei biologisch inaktivem Leptin oder Leptinmangel durch die Gabe von humanem rekombinantem Leptin verfügbar. Zudem gibt es mit dem MC4R -Agonisten (Setmelanotide) eine kausale Therapieoption für Patienten mit POMC-Mutation. Für Patienten mit Mutationen in MC4R, LEPR, PCSK1 finden aktuell klinische Studien hierzu statt, so dass in Zukunft eine kausale Therapie denkbar ist.

Summary

Though rare, it is important to identify patients with monogenic obesity in order to be able to offer them an optimized or even causal therapy. Hints for monogenic obesity are in particular extreme obesity, early onset obesity, as well as pathological eating-behaviour with hyperphagia, pronounced food seeking and lack of satiety. Mutations in genes of the leptinergic-melanocortinergicpathway lead to the main forms of monogenic obesity. Here, mutations in the melanocortin-4-receptor gene (MC4R) are the most common. A pronounced early childhood obesity occurs in autosomal recessive mutations in genes for leptin (LEP), leptin receptor (LEPR), pro-opiomelanocortin (POMC) and prohormone convertase 1/3 (PCSK1). Causal therapy is available for biologically inactive leptin or leptin-deficiency by the administration of human recombinant leptin. In addition, the MC4R agonist (Setmelanotide) provides a causal therapy for patients with POMC mutation. Clinical studies with this medication are currently undertaken for patients with mutations in MC4R, LEPR, PCSK1, so that causal therapy is conceivable in the future.

Schlüsselwörter

Monogene Adipositas - frühkindliche Adipositas - Leptin - Melanocortin-4-Rezeptor

Keywords

Monogenic obesity - early onset obesity - leptin - melanocortin-4-receptor.

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