Background

Amyloidosis is a name given to conditions characterized by accumulation of amyloid (proteinaceous deposits) in various tissues. In transthyretin amyloidosis, the most common hereditary form of amyloidosis, the amyloid material is transthyretin (TTR). The most common presentation of transthyretin amyloidosis is neuropathic, which typically manifests as autonomic or sensory motor impairment. Cardiac involvement is frequent in transthyretin amyloidosis is frequent and most often takes the form of restrictive cardiomyopathy. The enlarged appearance of the interventricular septum and left ventricular muscle reflects the deposition of TTR in these structures rather than true hypertrophy. The symmetrical pattern of enlargement and histological appearance help differentiate this condition from other forms of hypertrophic cardiomyopathy. Additional cardiac symptoms can include arrhythmias, congestive heart failure and sudden death. Variants in TTR are a primary cause of transthyretin amyloidosis and the disease has a high prevalence in certain ethnic groups, such as African Americans.

For more information about transthyretin amyloidosis, please visit GeneReviews.

Testing Strategy

TTR gene sequencing should be ordered for individuals with a clear or suspected diagnosis of TTR amyloidosis.

Methodology

This test is performed by Sanger sequencing of the coding regions and splice sites of the listed gene. This test does not detect large deletions or variants in non-coding regions that could affect gene expression.

Analytical and Clinical Sensitivity

This test is greater than 99.9% accurate in detecting variants in the sequence analyzed.

Sequencing of TTR detected more than 99% of disease-causing variant for transthyretin amyloidosis (GeneReviews).