Oculoleptomeningeal Amyloidosis Secondary to the Rare Transthyretin c.381T>G (p.Ile127Met) Mutation.

Abstract

Oculoleptomeningeal amyloidosis (OLMA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges along with ocular involvement. Of >100 TTR mutations identified, few have been associated with OLMA. Herein we describe the first report of leptomeningeal amyloidosis associated with the c.381T>G (p.Ile127Met) TTR mutation, linking this variant to the OLMA phenotype. A 53 year-old man presented with a 2-year history of progressive symptoms including upper and lower limb weakness, ataxia, and peripheral and autonomic neuropathy. Neuroimaging, including gadolinium-enhanced magnetic resonance imaging of the brain and spinal axis, identified diffuse leptomeningeal enhancement along the brainstem and spinal cord plus evidence of hemosiderosis. Pathologic and genetic analyses of biopsy material from enhancing intradural extramedullary tissue at the thoracolumbar junction was diagnostic of amyloidosis of a transthyretin type secondary to a TTR c.381T>G (p.Ile127Met) mutation. OLMA represents a rare subtype of heritable transthyretin amyloidosis that may present with progressive neurological decline secondary to central nervous system leptomeningeal amyloid deposition. This case identifies the c.381T>G (p.Ile127Met) TTR mutation variant as being implicated in the OLMA phenotype.