We aimed to characterize the peripheral nervous system involvement of hereditary transthyretin amyloidosis (hATTR) mutations in patients from three United States medical centers.

A retrospective, cross-sectional study was carried out on patients with genetically confirmed  V142I and other hATTR mutations at multiple institutions from 2018-2022. Neurologic, autonomic, and cardiac symptoms and signs, as well as electrodiagnostic study results, were reviewed for each patient.

Fifty-eight V142I and 18 non-V142I hATTR patients were evaluated. The majority of V142I patients had signs of PN, with abnormal pinprick sensation and temperature loss (74%), weakness (60%), and loss of dep tendon reflexes (59%). Presence of lightheadedness (29%) and gastro-intestinal symptoms (14%) suggested autonomic involvement. PN characteristics and prevalence of carpal tunnel syndrome did not differ significantly between V142I and non-V142I patients. The population of V142I patients was disproportionately African American (86 %) as expected. Ulnar motor nerve amplitude was significantly lower in V142I patients. Non V142i hATTR patients had lower left median motor amplitudes. Cardiac involvement was similar between  V142I patients and other hATTR mutations (72% vs. 88%).

Polyneuropathy is more commonly found in V142I hATTR patients than previously reported and has a wide range of phenotypic signs and symptoms. Only 30% of patients complained of neuropathic pain, which may have led to previous low estimates of PN in this population.  Electrodiagnostic studies were abnormal in most patients. A low threshold for neurology referral and electrodiagnostic studies in at-risk populations is encouraged.