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Abstract Details

Peripheral Nervous System Involvement of Hereditary Transthyretin Amyloidosis in the United States: A Multi-center Perspective
Neuromuscular and Clinical Neurophysiology (EMG)
S21 - Inherited Myopathies and Neuropathies: New Therapeutic Approaches and Observations (2:12 PM-2:24 PM)
007
HATTR is an autosomal dominant disease that occurs world-wide. The most common mutation in the United States, V142I, has previously been described as having a primarily cardiac presentation. However, the prevalence and neurodiagnostic characteristics of peripheral neuropathy (PN) in V142I hATTR patients is unclear.

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.

Authors/Disclosures
Hristelina Ilieva (ALS Weinberg Clinic)
PRESENTER
The institution of Dr. Ilieva has received research support from ALSA. The institution of Dr. Ilieva has received research support from Strategius. Dr. Ilieva has received personal compensation in the range of $500-$4,999 for serving as a reviewer with ALS Canada. Dr. Ilieva has received personal compensation in the range of $0-$499 for serving as a reviewer with DOD.
James Eyer Mr. Eyer has nothing to disclose.
Urvi Desai (Dept of Neurology, CMC) Dr. Desai has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Desai has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fulcrum. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Desai has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx.
Amanda Peltier (Vanderbilt University) Dr. Peltier has received personal compensation for serving as an employee of Alnylam. Dr. Peltier has received personal compensation for serving as an employee of Akcea. Dr. Peltier has received personal compensation for serving as an employee of CSL Behring. Dr. Peltier has received personal compensation for serving as an employee of Catalyst. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Akcea. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Csl Behring. Dr. Peltier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Akcea. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for catalyst. The institution of Dr. Peltier has received research support from NIH.