Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis

We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu 12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR, Clini cal features attributed to her leptomeningeal amyloid included radiculopath y, central hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and periods of decreased consciousness. MRT showed a marked enhan cement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy, The simultaneous presence of extensive visc eral amyloid and clinically significant deposits affecting both the periphe ral and central nervous system extends the spectrum of amyloid-related dise ase associated with TTR mutations. The unusual association of severe periph eral neuropathy with symptoms of leptomeningeal amyloid indicates that lept omeningeal amyloidosis should be considered part of the syndrome of TTR-rel ated familial amyloid polyneuropathy.