Transthyretin related amyloidosis (ATTR) results from the tissue deposition of misfolded mutant or wild-type transthyretin (TTR). Involvement of nervous system often heralds the onset of ATTR. Familial ATTR is because of mutations in the TTR gene which lead to destabilization of the tetrameric structure of TTR and generation of amyloidogenic monomers, tissue deposition of which causes end organ injury specially neuropathy and cardiomyopathy. Peripheral neuropathy is typically axonal with early involvement of the autonomic nerves. Wild-type TTR (ATTRwt), is a common cause of cardiomyopathy in the elderly and may play a role in the pathogenesis of carpal tunnel syndrome and spinal stenosis in that age group. Diagnosis of ATTR is made by demonstrating tissue amyloid deposits, then proving that the amyloid deposits consist of mutant or wild-type TTR, which necessitates assessment of TTR gene sequencing. Disease modifying treatments have become available for ATTR through liver transplantation, stabilization of the TTR molecule (diflunisal and tafamidis) and suppressing the gene expression of TTR (inotersen and patisiran).
Part of the book: Amyloid Diseases