Late-onset Hereditary Transthyretin Amyloidosis in Two Patients with Acquired Demyelinating Features

Abstract

Autosomal-dominant transthyretin (TTR)-related amyloidosis usually manifests in the third to fifth decade with a length-dependent axonal neuropathy and prominent involvement of the small diameter nerve fibers. Objectives: To describe the clinical and para-clinical findings in patients with hereditary transthyretin amyloidosis (hATTR), formerly known as transthyretin-related familial amyloid polyneuropathy (TTR-FAP). Methods: Electrodiagnostic, cerebrospinal fluid (CSF), and TTR gene findings in two patients misdiagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Results: A 78-year-old, right-handed, Caucasian male (patient 1) and a 69-year-old, right-handed, Japanese male (patient 2) were referred for late-onset sensory symptoms of the hands and feet as initial manifestations. The first patient, after several years, developed progressive leg weakness affecting his gait and balance, as well as dysautonomic complaints. The second patient had relatively rapid progression with bilateral foot drop and ambulation difficulty after a few months. In both patients, CSF findings were unremarkable. Lumbar spine magnetic resonance imaging did not reveal abnormal thickening or enhancement of the lumbar plexus and exiting nerve roots. Both patients were initially diagnosed with CIDP before being referred to our institution. Patient 2 was started on intravenous immunoglobulin by his primary neurologist, which was maintained for a year without a meaningful response. Repeat electrodiagnostic study at our institution revealed non-length-dependent axonal sensory loss and features of acquired demyelinating neuropathy. TTR gene testing identified pathogenic variants p.Val30Met or V30M, and p.Ala 117Ser or A117S, in the first and the second patient, respectively. Conclusion: hATTR can mimic CIDP clinically and electrodiagnostically. The presence of significant sensory axonal loss, rapid course, and lack of response to immunomodulation therapy should prompt consideration of this diagnosis and TTR gene testing.