Excerpt

Amyloidosis is a rare protein deposition disease caused by misfolding followed by tissue deposition of highly ordered aggregate proteins forming amyloid fibrils leading to progressive organ failure.1 Twenty-two different proteins have been reported to cause human disease.2 Systemic AL amyloidosis, caused by deposition of monoclonal immunoglobulin light chains, is the commonest type. Transthyretin (TTR), an inherently unstable tetrameric molecule, can deposit as amyloid fibril protein in the heart or the nerves. The wild-type molecule causes cardiac amyloidosis in the elderly (wtATTR amyloidosis or senile systemic amyloidosis) which is an increasingly recognized condition. Mutated TTR can cause familial amyloid cardiomyopathy (common in the African-American population due to deposition of variant TTR V122I)3,4 and much rarer autosomal dominant familial amyloid polyneuropathy due to other TTR mutations,5 some of which also cause significant cardiac amyloidosis. wtATTR amyloid deposits can be identified at autopsy in nearly a quarter of individuals over 80 years of age but the true incidence of clinically significant cardiac wtATTR amyloidosis remains unclear.6 TTR-V122I variant/polymorphism is seen in 4% of the African-American population and the penetrance is poor. The true incidence cardiac amyloidosis remains unclear. Mutations in Apolipoprotein A1 (AApoA1) is a rare cause hereditary cardiac amyloidosis. Cardiac involvement in all types of amyloidosis is the major cause of morbidity and mortality.7 …