Peripheral Nervous System Involvement of Hereditary Transthyretin Amyloidosis in the United States: A Multi-Center...

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant multisystem disorder that occurs worldwide. The most common mutation in the United States, V142I, has previously been described as having a primarily cardiac presentation. However, the prevalence of peripheral neuropathy (PN) in V142I ATTRv patients is unclear. We aimed to characterize and compare the peripheral nervous system involvement of the Val142Ile (V142I, previously V122I) ATTRv mutation with other known ATTRv mutations.

A retrospective, cross-sectional study was carried out on patients with genetically confirmed ATTRv at 3 institutions from 2018 to 2022. Neuropathic, autonomic, and cardiac symptoms and signs, as well as electrodiagnostic study results, were reviewed for each patient.

Fifty-eight V142I and eighteen non-V142I ATTRv patients were evaluated. The majority of V142I patients had signs of PN, with abnormal pinprick sensitivity and temperature loss (74%), weakness (60%), and loss of deep tendon reflexes (59%). The presence of lightheadedness (29%) and gastrointestinal symptoms (14%) suggested autonomic involvement. PN characteristics and the prevalence of median mononeuropathy did not differ significantly between V142I and non-V142I patients. The population of V142I patients was disproportionately African American (86%) as expected.

Polyneuropathy is more commonly found in V142I ATTRv patients than previously reported and has a wide range of phenotypes. A low threshold for neurology referral and electrodiagnostic studies in at-risk populations is encouraged.