Clinical Information

The systemic amyloidoses include a number of disorders of varying etiology characterized by extracellular protein deposition. The most common form is an acquired amyloidosis secondary to multiple myeloma or monoclonal gammopathy of unknown significance in which the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of proteins. There are also hereditary forms of amyloidosis. Due to the clinical overlap between the acquired and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and consider appropriate therapeutic interventions.

The most common hereditary amyloidosis is familial transthyretin amyloidosis, an autosomal dominant disorder caused by variants in the transthyretin (TTR) gene. The resulting amino acid substitutions lead to a relatively unstable, amyloidogenic TTR protein. Most individuals begin to exhibit clinical symptoms between the third and seventh decades of life. Typically, TTR-associated amyloidosis is progressive over a course of 5 to 15 years, and the most common cause of death is cardiomyopathy. Affected individuals may present with a variety of symptoms, including peripheral neuropathy, blindness, cardiomyopathy, nephropathy, autonomic nervous dysfunction, or bowel dysfunction.

It is important to note that this assay does not detect variants associated with non-TTR forms of familial amyloidosis.