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We report a novel transthyretin variant, Gly53Ala, in a 44-year-old British woman who presented with severe episodic headaches, often with focal neurological deficit, before developing progressive ataxia, depression, dementia and eventually peripheral neuropathy. Transthyretin amyloidosis was confirmed on biopsy of the heart muscle. Serum amyloid P component scintigraphy did not show visceral amyloid in extra-cardiac sites, but magnetic resonance imaging indicated diffuse leptomeningeal amyloidosis.

A novel amyloidogenic transthyretin variant, Gly53Ala, associated with intermittent headaches and ataxia