C-terminal TTR fragments are often present in amyloid-laden tissues of most patients with ATTRamyloidosis, and on the basis of <i>in vitro</i> studies, these fragments have been proposed to play important roles in amyloid formation.
Although not described previously, elevated IOP may develop in patients with vitreous amyloidosis due to a TTRVal30Gly mutation in the transthyretin gene.
Hereditary ATTRV30Mamyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR).
This review will focus on the key findings of the structural studies of TTR that provided atomic level description of its architecture, the mechanistic role of structural components involved in its function and misfolding, and the progress and limitations towards the design of selective inhibitors for TTRamyloidoses.
The stabilizers and/or the amyloid fibril disrupters isolated from natural sources may become lead compounds for the treatment of TTR-related amyloidosis.
This case illustrated the clinical and pathologic phenotype of an ATTRamyloidosis patient who initially presented impaired renal function and p.Leu75Pro variant was found by sequencing the coding region of TTR gene.
Moreover, as there are specific therapies for some forms of HCM including enzyme substitution and chaperone therapies and specific treatments for TTRamyloidosis, a differential diagnosis should be sought in all patients with unexplained left ventricular hypertrophy.
Assessment of myocardial uptake of Tc-99m-pyrophosphate (Tc-99m PYP) is pivotal in distinguishing transthyretin-associated cardiac amyloidosis (ATTR) from light chain amyloid (AL).
Therefore, we and other ATTR amyloidosis research groups have been investigating the possibility of stabilization of variant TTR, gene therapy, and immunotherapy for ATTR amyloidosis on the basis of TTRamyloid formation mechanism.
Three methods of quantitation were developed and tested on 74 patients with proven cardiac ATTRamyloidosis who had recently undergone <sup>99m</sup>Tc-DPD planar whole-body imaging and SPECT-CT. Quantitative results were compared to measurements of extracellular volume fraction (ECV) by cardiac magnetic resonance imaging, a validated technique for measuring amyloid burden.
(99m)Tc-DPD uptake was also absent (score of 0) among unaffected controls and in 2 unaffected relatives of patients with hereditary transthyretin-related amyloidosis who harbor a mutation in the TTR gene.
Predominant symptom presentation in patients with hereditary TTRamyloidosis differed according to the underlying disease-causing mutation (polyneuropathy for Val30Met, cardiomyopathy for Val122Ile and Leu111Met, and mixed for Glu89Gln).
Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion.
It summarizes the data about therapies for light chain amyloidosis including bortezomib regimens and also novel disease modifying therapies for ATTRamyloidosis such as gene silencers, transthyretin stabilizers, and degraders of amyloid fibrils.
Patients with hereditary ATTRamyloidosis occasionally show electrophysiological demyelinating features without conduction block following severe axonal degeneration.