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Review
. 2020 Feb 21:16:109-123.
doi: 10.2147/TCRM.S219979. eCollection 2020.

Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care

Marco Luigetti  1   2 , Angela Romano  2 , Andrea Di Paolantonio  2 , Giulia Bisogni  3 , Mario Sabatelli  2   3
Affiliations
Review

Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care

Marco Luigetti et al. Ther Clin Risk Manag. .

Abstract

Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy) is a rare disease due to mutations in the gene encoding transthyretin (TTR) and characterized by multisystem extracellular deposition of amyloid, leading to dysfunction of different organs and tissues. hATTR amyloidosis represents a diagnostic challenge for neurologists considering the great variability in clinical presentation and multiorgan involvement. Generally, patients present with polyneuropathy, but clinicians should consider the frequent cardiac, ocular and renal impairment. Especially a hypertrophic cardiomyopathy, even if usually latent, is identifiable in at least 50% of the patients. Therapeutically, current available options act at different stages of TTR production, including synthesis inhibition (liver transplantation and/or gene-silencing drugs) or tetramer TTR stabilization (TTR stabilizers), increasing survival at different disease stages.

Keywords: amyloid; clinical care; polyneuropathy; therapy; transthyretin.

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Conflict of interest statement

Dr Luigetti received financial grants (honoraria and speaking) from Akcea, Alnylam and Pfizer, and travel grants from Pfizer, Kedrion and Grifols; Dr Bisogni received financial grants (honoraria and speaking) from Alnylam, and travel grants from Pfizer, and Grifols; Dr Romano received travel grants from Akcea and Pfizer; Dr Di Paolantonio received travel grants from Akcea and Pfizer; Dr Sabatelli received financial grants (honoraria and speaking) from Akcea. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Multisystem involvement in hATTR.
Figure 2
Figure 2
Sural nerve biopsies from a patient with late-onset FAP. Semithin sections stained with toluidine blue showed a severe reduction of myelinated fibres (A). A second biopsy performed four years later revealed complete loss of myelinated fibres (B), while unmyelinated fibres were relatively preserved (C).
Figure 3
Figure 3
Sural nerve biopsy from a patient with late-onset FAP. Congo red staining showed a small amyloid deposition (A). Ultrastructural analysis with electron microscope confirmed short and thin amyloid fibrils (B).
Figure 4
Figure 4
Sural nerve biopsy from a patient with late-onset FAP. Semithin section stained with Toluidine blue (A) showed amyloid deposition, also confirmed by H&E (B) and Congo red (C) staining. However, immunofluorescence with anti-TTR (D), anti-kappa light chain (E), and anti-lambda light chain (F) resulted not specific for TTR amyloidosis.
Figure 5
Figure 5
Flow-chart strategy for the diagnosis of FAP in endemic (left) and non-endemic (right) areas.
Figure 6
Figure 6
Overview of therapeutic strategies in hATTR with polyneuropathy.
None
See this image and copyright information in PMC

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