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Humangenetik beim atypischen hämolytisch-urämischen Syndrom – Rolle in Diagnostik und Therapie

Human genetics in atypical hemolytic uremic syndrome—its role in diagnosis and treatment

  • Schwerpunkt: Genetik in der Inneren Medizin
  • Published:
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Zusammenfassung

Das atypische hämolytisch-urämische Syndrom (aHUS) als eine der drei Hauptformen der thrombotischen Mikroangiopathie ist gekennzeichnet durch genetische Veränderungen im Bereich der Komplementkaskade. Diese lassen sich bei 40–60 % aller Patienten mit aHUS nachweisen. Mittlerweile sind Mutationen in über 10 verschiedenen Genen identifiziert worden. Am häufigsten und klinisch relevantesten sind Mutationen, die zu einer verminderten oder fehlenden Funktion von Faktor H, zur Bildung von Hybridgenen oder zur Bildung von Autoantikörpern gegen Faktor H führen. Für die Diagnosestellung wird keine genetische Untersuchung benötigt, allerdings ist sie für die Therapiesteuerung von großer Bedeutung, so etwa bei der Entscheidung, wie lange mit dem C5-Inhibitor Eculizumab behandelt werden muss. Auch ist die Kenntnis der genetischen Veränderungen absolut erforderlich, wenn eine Verwandtenlebendspende erwogen wird, um den Lebendspender und Empfänger vor einem aHUS bewahren zu können.

Abstract

The atypical hemolytic uremic syndrome (aHUS), one of the three major forms of thrombotic microangiopathy, is characterized by genetic alterations in the area of the complement cascade, which can be detected in 40%–60% of all patients with aHUS. Mutations in over 10 different genes have now been identified. The most frequent and clinically relevant of these are mutations that result in a decreased or absent function of factor H, the formation of hybrid genes, or the formation of autoantibodies against factor H. Although genetics are not required for the diagnosis of aHUS, it is of great importance for the decision on how long to treat with the C5 inhibitor eculizumab. Also, knowledge of genetic alterations is absolutely essential if a living related donor is considered, in order to protect the living donor and recipient from developing aHUS.

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Authors and Affiliations

  1. Klinik für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    M. Knoop, H. Haller &  J. Menne

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  1. M. Knoop
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  2. H. Haller
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  3. J. Menne
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Correspondence to J. Menne.

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Interessenkonflikt

M. Knoop gibt an, dass kein Interessenkonflikt besteht. H. Haller und J. Menne haben von der Firma Alexion, die Eculizumab zur Behandlung von Patienten mit aHUS herstellt, Beratungs- oder Vortragshonorare erhalten.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Redaktion

H. Haller, Hannover

G. Hasenfuß, Göttingen

J.R. Schäfer, Marburg

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Knoop, M., Haller, H. & Menne, J. Humangenetik beim atypischen hämolytisch-urämischen Syndrom – Rolle in Diagnostik und Therapie. Internist 59, 799–804 (2018). https://doi.org/10.1007/s00108-018-0455-9

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  • DOI: https://doi.org/10.1007/s00108-018-0455-9

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