Hereditary transthyretin amyloidosis overview

Fiore Manganelli, Gian Maria Fabrizi, Marco Luigetti, Paola Mandich, Anna Mazzeo, Davide Pareyson

Research output: Contribution to journalReview articlepeer-review


Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis is a rare autosomal dominantly inherited disorder caused by mutations in the transthyretin (TTR) gene. The pathogenetic model of ATTRv amyloidosis indicates that amyloidogenic, usually missense, mutations destabilize the native TTR favouring the dissociation of the tetramer into partially unfolded species that self-assemble into amyloid fibrils. Amyloid deposits and monomer-oligomer toxicity are the basis of multisystemic ATTRv clinical involvement. Peripheral nervous system (autonomic and somatic) and heart are the most affected sites. In the last decades, a better knowledge of pathomechanisms underlying the disease led to develop novel and promising drugs that are rapidly changing the natural history of ATTRv amyloidosis. Thus, clinicians face the challenge of timely diagnosis for addressing patients to appropriate treatment. As well, the progressive nature of ATTRv raises the issue of presymptomatic testing and risk management of carriers. The main aim of this review was to focus on what we know about ATTRv so far, from pathogenesis to clinical manifestations, diagnosis and hence patient’s monitoring and treatment, and from presymptomatic testing to management of carriers.

Original languageEnglish
JournalNeurological Sciences
Publication statusAccepted/In press - 2020


  • Amyloidosis
  • ATTRv
  • Transthyretin
  • TTR

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health


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