A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis.

Leptomeningeal amyloidosis is a rare central nervous system manifestation of systemic amyloidosis from transthyretin (TTR) mutation. Ten TTR gene mutations associated with this condition have been described. We report the clinical, radiological, and pathological features of a case of leptomeningeal amyloidosis from a novel Thr49Pro TTR gene mutation. A 53 year-old man presented with recurrent episodes of transient aphasia and right hand stiffness, headaches, and peripheral neuropathy. A surgical biopsy of the leptomeninges and superficial cortex, and DNA sequences of the TTR gene were analyzed. Elevated cerebrospinal fluid (CSF) protein and diffuse leptomeningeal enhancement of the neuraxis from the cortical sulci to the cauda equina on contrast MRI were the defining clinical features. A surgical biopsy revealed TTR amyloid deposition in the subpia and within the leptomeningeal blood vessels. DNA sequencing showed a proline-for-threonine substitution at codon 49 of the TTR gene in one allele. A novel Thr49Pro TTR gene mutation is associated with leptomeningeal amyloidosis resulting in recurrent CNS symptoms.