Key Information
Hereditary transthyretin (hATTR) amyloidosis is a rare, systemic, progressive, debilitating, and fatal disease characterized by mutations in the gene encoding the transthyretin (TTR) protein. More than 130 reported TTR gene mutations promote misfolding of TTR proteins, which aggregate and deposit as insoluble amyloid deposits in tissues, inducing organ damage. Worldwide prevalence estimates indicate that approximately 50,000 people have been diagnosed with hATTR amyloidosis, although it is thought to be significantly underdiagnosed. Patients with hATTR amyloidosis typically suffer peripheral and autonomic nerve fiber injury, resulting in a length-dependent sensorimotor peripheral neuropathy, manifesting as pain, numbness, and weakness with eventual loss of ambulation. Others experience cardiomyopathy, characterized by conduction disease, thickening and stiffening of the ventricles, and eventual heart failure. The majority of patients, however, exhibit a mixed phenotype including nerve- and heart-related manifestations.