Wild-Type ATTR Amyloidosis

In wild-type transthyretin (TTRwt) amyloidosis, transthyretin gene (TTR) has a normal sequence without any variants. TTR is mainly produced by the liver, and its main aim is the transport of thyroid hormone and retinol. TTR is formed by four identical monomers stabilized by hydrogen bonds and hydrophobic interactions. The triggers of the amyloidogenic process in ATTRwt are still unclear; however, amyloidogenesis starts with the tetramer dissociation followed by the monomers misfolding and aggregation into oligomers and fibrils. In ATTRwt, heart and musculoskeletal soft tissues are the structures in which TTR fibrils are more frequently deposited. Amyloid deposition can affect every cardiac structure and may lead to the development of a pseudo-hypertrophic phenotype, heart failure with preserved and subsequently a reduced ejection fraction, and arrhythmias such as atrial fibrillation or conduction disturbances. The musculoskeletal soft tissues may be infiltrated early, on average 5–15 years before cardiac manifestations. The most frequent orthopedic manifestations include: carpal tunnel syndrome, brachial biceps tendon rupture, lumbar spinal stenosis, joint replacement (hip, knee, and shoulder), and trigger finger. Affected patients are usually diagnosed after the age of 70 and predominantly males. The association of cardiac and musculoskeletal manifestations in this population should promptly rise the suspect for ATTRwt.