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Schwere Hypertriglyzeridämie

Diagnostik und neue Therapieprinzipien

Severe hypertriglyceridemia

Diagnostics and new treatment principles

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Zusammenfassung

Schwere Hypertriglyzeridämien liegen ab Triglyzerid(TG)-Werten von >885 mg/dl vor. Ursache sind häufig sog. „Large-variant“-Mutationen in Genen, die die Funktion der Lipoproteinlipase (LPL) beeinflussen – insbesondere bei einem Auftreten vor dem 40. Lebensjahr. Grundsätzlich sind sekundäre Faktoren diagnostisch auszuschließen oder entsprechend zu behandeln, bevor eine weitere molekulargenetische Diagnostik durchgeführt wird. Klinisch fast immer typisch sind rezidivierende, zum Teil starke abdominale Schmerzen, die sich zu einer akuten Pankreatitis entwickeln können, der wichtigsten und in manchen Fällen lebensgefährlichen Komplikation. Zur Minimierung des Pankreatitisrisikos ist ein TG-Wert <1000 mg/dl anzustreben. Andere Symptome, die ebenfalls auftreten können und reversibel sind, sind eruptive Xanthome, Lipaemia retinalis, Hepatosplenomegalie, Dyspnoe und neurokognitive Einschränkungen. Die Hyperchylomikronämie führt zu einer Hyperviskosität des Blutes, was als Ursache für einige der obigen Symptome gesehen wird. Milde bis moderate Hypertriglyzeridämien gehen mit einer Erhöhung des kardiovaskulären Risikos einher, dessen Senkung das primäre Therapieziel ist. Die Grundlage der Therapie bilden eine lebenslange, streng fett- und kohlenhydratreduzierte Diät und Alkoholkarenz. Omega‑3-Fettsäuren und Fibrate werden zur TG-Senkung eingesetzt. Neue gentherapeutische Ansätze stehen seit Kurzem in Deutschland für Patienten mit LPL-Defizienz zur Verfügung.

Abstract

Severe hypertriglyceridemia is defined at a plasma triglyceride (TG) concentration of >885 mg/dl and may result – in particular when clinical symptoms appear before the age of 40 – from “large variant” mutations in genes which influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary factors have to be excluded and treated before further genetic tests are considered. Typical symptoms in almost all patients are recurrent, sometimes severe abdominal pain attacks, which can result in acute pancreatitis, the most important, sometimes life-threatening complication. To minimize the risk of severe pancreatitis, the aim is to maintain the plasma TG concentration <1000 mg/dl. Other clinical manifestations which can occur and are reversible are eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, dyspnea syndrome, and impaired neurocognitive function. The hyperviscosity syndrome caused by chylomicronemia is seen as the underlying reason for some of the symptoms. Patients with mild-to-moderate hypertriglyceridemia have an increased cardiovascular risk. To lower this is the primary treatment goal here. Treatment mainly consists of a life-long, strict fat- and carbohydrate-restricted diet and the abstention from alcohol. Omega‑3-Fatty acids and fibrates can be used to lower plasma TG levels. Recently, new gene therapy approaches for LPL-deficient patients have become available in Germany.

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Authors and Affiliations

  1. Charité, Universitätsklinik Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    U. Kassner &  E. Steinhagen-Thiessen

  2. MD Medscript & -consult, Am Kuhtriftberg 21, 67098, Bad Dürkheim, Deutschland

    M. Dippel

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U. Kassner und E. Steinhagen-Thiessen geben an, dass kein Interessenkonflikt besteht. M. Dippel (MD Medscript & -consult) wurde für die Erstellung des Manuskripts von der Firma uniQure finanziell unterstützt.

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

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Kassner, U., Dippel, M. & Steinhagen-Thiessen, E. Schwere Hypertriglyzeridämie. Internist 58, 866–876 (2017). https://doi.org/10.1007/s00108-017-0234-z

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