Amyloid Light Chain (AL) Amyloidosis

Amyloid light chain (AL) amyloidosis is one of the most frequent forms of amyloidosis. In this condition, a plasma cell clone produces monoclonal immunoglobulin light chains that are structurally unstable, then prone to misfolding and exposing “sticky” residues that form insoluble amyloid fibrils. Due to high presenting levels of the light chains, the equilibrium between synthesis and degradation is broken, and an explosive reaction of unfolded proteins forms protofibrils and then fibrils lead to progressive end organ damage. The heart and kidneys are the most frequently affected organs. In addition to altering tissue structure and functioning, light chains may have direct toxic proteotoxicity, particularly in the heart. Cardiac involvement is associated with a worse prognosis, and majority of patients present with advanced disease—early diagnosis remains elusive. The key steps are to prove and type the amyloid deposits, determine the monoclonal protein and free light chains, and assess the disease stage with natriuretic peptides and troponin. In those with monoclonal gammopathies of uncertain significance or smoldering myeloma, or when heart failure symptoms are present, cardiac biomarkers and urine for albuminuria may offer easy tools for early diagnosis. The occurrence of low voltages or pathological Q waves on electrocardiogram, together with the evidence of pseudohypertrophy on echocardiogram, supports the execution of further examinations such as cardiac magnetic resonance. The combination of three biomarkers (troponin, natriuretic peptides, and free light chains) also allows to predict patient risk and define the best therapeutic strategy.