Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis

Antonia Carroll, P. James Dyck, Mamede de Carvalho, Marina Kennerson, Mary M. Reilly, Matthew C. Kiernan, Steve Vucic

Research output: Contribution to journalReview articlepeer-review


Hereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney and the eyes. ATTRv is caused by mutations of the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. Typically, the neuropathy associated with ATTRv is characterised by a rapidly progressive and disabling sensorimotor axonal neuropathy with early small-fibre involvement. Carpal tunnel syndrome and cardiac dysfunction frequently coexist as part of the ATTRv phenotype. Although awareness of ATTRv polyneuropathy among neurologists has increased, the rate of misdiagnosis remains high, resulting in significant diagnostic delays and accrued disability. A timely and definitive diagnosis is important, given the emergence of effective therapies which have revolutionised the management of transthyretin amyloidosis. TTR protein stabilisers diflunisal and tafamidis can delay the progression of the disease, if treated early in the course. Additionally, TTR gene silencing medications, patisiran and inotersen, have resulted in up to 80% reduction in TTR production, leading to stabilisation or slight improvement of peripheral neuropathy and cardiac dysfunction, as well as improvement in quality of life and functional outcomes. The considerable therapeutic advances have raised additional challenges, including optimisation of diagnostic techniques and management approaches in ATTRv neuropathy. This review highlights the key advances in the diagnostic techniques, current and emerging management strategies, and biomarker development for disease progression in ATTRv.

Original languageEnglish (US)
Pages (from-to)668-678
Number of pages11
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number6
StatePublished - 2022

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery


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