To describe the prevalence of neurological manifestations in patients with a wide variety of genetic mutations of hereditary transthyretin amyloidosis (hATTR) at a major multidisciplinary amyloidosis center.

hATTR amyloidosis is a clinically heterogeneous disease with various neurological, cardiac and other manifestations. Better characterization of neurological findings is critical for earlier diagnosis in an era when several therapies for amyloidosis are becoming commercially available.

A retrospective chart review of all consecutive patients evaluated at a single United States Amyloidosis Center between January 1, 2016 to December 31, 2018 was performed. Variables coded included genetic mutation, neurological symptom manifestations (e.g. symptoms attributable to large fiber polyneuropathy, small fiber neuropathy or dysautonomia), physical examination findings (e.g. distal weakness, dissociative sensory loss, macroglossia), prior neurophysiological testing, relevant spinal imaging and others.

The most common genetic mutations in the 92 patients in the study included V122I (36), T60A (20), V30M (12), L58H (5), F64L (3), Y114C (3), S77Y (2). Eleven other mutations had a prevalence of one. The prevalence of symptoms and signs of large fiber neuropathy were 66% and 75% respectively. The prevalence of symptoms and signs of small fiber neuropathy were 36% and 65% respectively. Cervical and lumbar stenosis or radiculopathy were present in 11% and 18% of patients respectively. Symptoms attributed to dysautonomia were found in 47%, symptoms of CTS in 73%, unexplained dysphagia in 11% and macroglossia in 3%.

hATTR amyloidosis is a multiorgan disease with various neurological manifestations. Although clinical presentations are heterogeneous, an understanding of neurological symptomatology may prompt earlier diagnosis and help clinicians predict clinical course based on genetic mutation.