ATTRV122I amyloidosis

Familial amyloid cardiomyopathy

Familial amyloid cardiomyopathy (FAC), or transthyretin amyloid cardiomyopathy, also called ATTR-CM is a heart muscle disease. A misshapen protein, transthyretin, builds up in the heart. It can also affect the nerves and other parts of the body. The condition is potentially fatal and often underdiagnosed. It causes stiffening of the walls of the heart, especially affecting the left ventricle, leading to cardiomyopathy and eventually heart failure. The condition results from the aggregation and deposition of mutant and wild-type transthyretin (TTR) protein in the heart. TTR is usually circulated as a homo-tetramer—a protein made up of four identical subunits—however, in FAC populations, TTR dissociates from this typical form and misassembles into amyloid fibrils which are insoluble and resistant to degradation. Due to this resistance to degradation, when amyloid fibrils accumulate in the heart's walls, specifically the left ventricle, rigidity prevents the heart from properly relaxing and refilling with blood: this is called diastolic dysfunction, which can ultimately lead to heart failure.