Hereditary Transthyretin-Related Amyloidosis | oneAMYLOIDOSISvoice

Trusted Resources: Education

Scientific literature and patient education texts

Hereditary Transthyretin-Related Amyloidosis

key information

source: Acta Neurologica Scandinavica

year: 2019

authors: Finsterer J, Iglseder S, Wanschitz J, Topakian R, Löscher WN, Grisold W


Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation.

TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy.

If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal).

organization: Krankenanstalt Rudolfstiftung, Austria; Konventhospital Barmherzige Brüder, Austria; Medical University Innsbruck, Austria; Klinikum Wels-Grieskirchen, Austria; Ludwig Boltzmann Institute for Experimental und Clinical Traumatology, Austria

DOI: 10.1111/ane.13035

read more full text

To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences.
More information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.