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

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.

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

“…A possible cross-reaction among antibodies for amyloid typing has been described [11], and it confirms the importance of excluding hATTR through genetic testing when amyloid light-chain (AL) amyloidosis is suspected. On the other hand, in the other two cases, a MGUS was present, and a concomitant AL was diagnosed, confirming the importance of typing amyloid deposits [12].…”

“…However, because of the patchy distribution of amyloid fibrils in tissues, a negative biopsy does not rule out the diagnosis, and multiple biopsies might be necessary in some cases. Furthermore, biopsy sensitivity depends on multiple factors, such as pathologist experience, the biopsied tissue, and the patient's age [4,11,12].…”

Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis: a Single-Centre Experience

“…Hereditary transthyretin (ATTR) amyloidosis is a rare disease due to mutations in the gene encoding transthyretin (TTR) and characterized by multisystem extracellular deposition of amyloid, leading to a dysfunction of different organs and tissues [1]. To date, more than 100 TTR variants have been described as a cause of hereditary ATTRv amyloidosis, the most frequent being the Val30Met mutation [2].…”

“…Hereditary ATTRv amyloidosis represents a diagnostic challenge to clinicians considering the great variability in the clinical presentation and multiorgan involvement. Generally, patients present with polyneuropathy, but clinicians should consider the frequent cardiac, ocular, and gastrointestinal (GI) impairment [1,3,4]. However, the pattern of the clinical impairment may vary according to the geographic areas.…”

The Clinical and Economic Burden of Newly Diagnosed Hereditary Transthyretin (ATTRv) Amyloidosis: A Retrospective Analysis of Claims Data

“…However, transplant is associated with risks, such as morbidity due to chronic immunosuppression, and has been shown to be ineffective in the long-term improvement of quality of life and slowing of disease progression [1,16,17]. Several novel pharmacological options have been showing efficacy for treating early stages of ATTRv amyloidosis, including TTR stabilizers (e.g., tafamidis, diflunisal), RNA interference (RNAi) therapy (e.g., patisiran), and antisense oligonucleotides (e.g., inotersen) [18]. The above options, minus tafamidis, have been approved and are available for use in the USA.…”