Variant Transthyretin Amyloidosis (ATTRv) neuropathy is an
adult-onset, autosomal dominant, lethal, multisystemic disease due to the
deposition of mutated transthyretin (TTR) in various organs, commonly
involving the peripheral nerves and the heart. Circulating TTR tetramers are
unstable due to the presence of mutated TTR and dissociate into monomers,
which misfold and form amyloid fibrils. Although there are more than 140
mutations in the TTR gene, the p.Val50Met mutation is by far the
commonest. In the typical, early-onset cases, it presents with a small sensory
fibre and autonomic, length-dependent, axonal neuropathy, while in late-
onset cases, it presents with a length-dependent sensorimotor axonal
neuropathy involving all fibre sizes. Its treatment is now available and
includes TTR stabilizers, TTR amyloid removal as well as gene silencing,
while gene editing therapies are on the way. Its timely diagnosis is of
paramount importance for a better prognosis.