E-Pearl of the Week: Transthyretin amyloidosis

August 23, 2012


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Brought to you by the Resident and Fellow Section of Neurology®.

August 22, 2012

Transthyretin amyloidosis

Familial amyloid polyneuropathies are secondary to amyloid deposits in the peripheral nervous system as a result of misfolding of mutant proteins such as transthyretin (TTR), apolipoprotein A–1, or gelsolin. The most common variety of FAP is due to dominantly inherited TTR gene mutations which are particularly prevalent in Portugal, Sweden and Japan. Patients usually present in their thirties with a distal painful sensory neuropathy followed by motor and pronounced autonomic dysfunction. Patients may benefit from liver transplantation because the mutated TTR is primarily generated in the liver. Tafamidis, a drug that may be beneficial to patients with TTR amyloidosis,  occupies TTR's thyroxine binding sites, stabilizes mutated TTR tetramers and prevents misfolding of the protein.


1. Yamashita T, Ando Y, Okamoto S, et al. Long–term survival after liver transplantation in patients with familial amyloid polyneuropathy. Neurology 2012;78: 637–643.
2.  Hammarström P, Wiseman RL, Powers ET, Kelly JW. Prevention of transthyretin amyloid disease by changing protein misfolding energetics. Science 2003;299: 713–716.
3. Coelho T, Maia L, Martins da Silva A, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 2012; 79: 785–792.

Submitted by: Chafic Karam, MD

Disclosures: Dr. Karam serves on the editorial team for the Neurology® Resident and Fellow Section.

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