Transthyretin-Related Familial Amyloid Polyneuropathy: In the Light of New Developments/Yeni Gelismeler Isiginda Transtiretin Iliskili Ailevi Amiloid Polinoropatisi

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is caused by gain-of-toxic-function of TTR, which dissociates from its native tetramer form to a monomer form and aggregates in several tissues and organs. Mutations in the TTR gene lead to this amyloidogenic transformation and cause autosomal dominant disease. TTR-FAP typically causes sensorimotor FAP accompanied by autonomic involvement, but considerable phenotypic diversity is noted between different mutation types. In the event of clinical suspicion, TTR gene sequencing and pathologic confirmation are the recommended paths to follow. Significant improvement has been achieved in treating the disease over the past 20 years, starting with liver transplantation, followed by tetramer stabilizers and TTR-lowering therapies. Although there are still some uncertainties in diagnosing and treating TTR-FAP, recent advances are promising, especially in the field of treatment. Keywords: Amyloidosis, transthyretin, polyneuropathy, genetics, neuropathy Oz Transiretin iliskili ailevi amiloid polinoropatisi (TTR-FAP), vucutta tetramer formda bulunan TTR'nin monomer hale gelerek toksik ozellik kazanmasi ve cesitli doku ve organlarda birikmesi sonucunda gelisir. TTR genindeki mutasyonlar, proteine amiloidojenik ozellik kazandirmakta ve otozomal dominant gecisli hastaliga neden olmaktadir. TTR-FAP tipik olarak otonom tutulumun eslik ettigi sensorimotor noropatiye neden olur, ancak farkli mutasyon tipleri arasinda ciddi fenotipik farklilik belirtilmistir. Klinik suphe halinde genetik ve patolojik inceleme yapilmasi gerekmektedir. Son 20 yilda, karaciger transplantasyonu ile baslayan, tetramer stabilizatorlerin ve TTR yapimini baskilayan ilaclarin klinik calismalarda ciddi etkisinin gosterilmesi ile devam eden surecte tedavi acisindan onemli yol alinmistir. Hastaligin tani ve tedavisinde hala bazi belirsizlikler olmakla birlikte, ozellikle tedavi alanindaki son gelismeler umit vericidir. Anahtar Kelimeler: Amiloidoz, transtiretin, polinoropati, genetik, noropati