Abstract 11627: Genetic Testing for Hereditary Amyloid Transthyretin Amyloidosis: Insights From the Compass Program

Introduction: Hereditary amyloid transthyretin (hATTR, or ATTRv [variant]) amyloidosis is a progressive and fatal disease caused by alterations in the transthyretin ( TTR ) gene that result in the deposition of misfolded protein throughout the body, leading to multisystem dysfunction. The p.V142I and p.T80A pathogenic alterations typically manifest with a cardiac phenotype, and early diagnosis is crucial to achieving optimal patient outcomes. The hATTR Compass Program offers confidential genetic testing to patients suspected of having hATTR in the United States, Canada, and Puerto Rico. Methods: Patients were referred to Compass for genetic testing using a TTR single-gene analysis, a cardiovascular-focused 92-gene panel, or a neuropathy-focused 81-gene panel. All patient demographics were self-reported. This report analyzes patients with TTR alterations. Results: A total of 22,801 patients were referred for genetic testing; 1469 (6%) patients were positive for TTR . Of those, 1237 (84%) had the p.V142I alteration and 73 (5%) had the p.T80A alteration. Patients with p.V142I were predominantly Black (81%), while patients with p.T80A were predominantly White (86%). Most p.V142I patients were male (60%), while 48% of p.T80A patients were male. The average age at testing was earlier in patients with p.T80A (56 y) compared with p.V142I (67 y). The majority of p.T80A patients reported a family history of ATTR (64%), contrasting with only 23% of p.V142I patients. In patients with p.V142I and p.T80A who reported symptoms (1049 vs 42, respectively), most reported heart disease (90% vs 71%). Other symptoms included bilateral carpel tunnel syndrome (24% vs 31%), renal issues (22% vs 12%), and gastrointestinal issues (9% vs 31%). Patients with p.T80A reported a higher incidence of sensory (52%), motor (31%), and autonomic (29%) dysfunction compared with patients with p.V142I (31%, 18%, and 21%, respectively). Conclusions: Patients with p.V142I were mostly Black and were less likely to have a known family history of hATTR. Both p.V142I and p.T80A patients presented with mixed symptoms, including heart disease and polyneuropathies. Genetic testing may be an efficient path toward early diagnosis and treatment for this progressive and fatal disease.