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Hereditäre Transthyretin-Amyloidosen

Hereditary transthyretin amyloidosis

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Zusammenfassung

Hereditäre Amyloidosen sind autosomal-dominant vererbte Multisystemerkrankungen mit fatalem Ausgang, die auf extrazellulären Ablagerungen fehlgefalteter Eiweiße beruhen. Sie sind daher als erblich bedingte Proteinfaltungs- und -ablagerungskrankheiten aufzufassen, die progrediente Organschäden verursachen und schließlich zum Tode führen. Häufigste Ursache sind Mutationen im Transthyretin-Gen. Hauptmanifestation ist eine chronisch-progrediente axonale sensomotorische und autonome Polyneuropathie (familiäre Amyloidpolyneuropathie, FAP). Eine kardiale Beteiligung ist bei der FAP häufig, charakteristisch ist weiterhin der Befall von Darm und Augen. Bei einigen Mutationen steht der Herzbefall im Vordergrund (familiäre Amyloidkardiomyopathie, FAC). Therapeutisch wird seit 25 Jahren die orthotope Lebertransplantation vorgenommen, seit kurzem steht mit der Substanz Tafamidis auch ein Transthyretin-Stabilisator für Patienten mit symptomatischer Polyneuropathie im Stadium 1 zur oralen Therapie zur Verfügung. Weitere Therapieoptionen werden derzeit in Studien untersucht.

Summary

Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. E. Hund ist Vorsitzender der Deutschen Gesellschaft für Amyloidkrankheiten (DGAK) und hat Honorare für Vorträge und Reisekostenzuschüsse von der Fa. Pfizer erhalten. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Neurologische Klinik, Universität Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland

    E. Hund

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Hund, E. Hereditäre Transthyretin-Amyloidosen. Nervenarzt 85, 1291–1297 (2014). https://doi.org/10.1007/s00115-014-4133-4

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  • DOI: https://doi.org/10.1007/s00115-014-4133-4

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