Abstract Details

Title Unravelling Pheno-Genotypic Associations in Transthyretin Amyloidosis Using Data from THAOS [mdash] The Transthyretin Amyloidosis Outcomes Survey

Topic Peripheral Nerve

Presentation(s) P05 - (-)

Poster/Presentation
Number 062

Objective

Background BACKGROUND: There is great heterogeneity in TTR amyloidosis, with over 100 known pathogenic mutations of the TTR protein, and considerable phenotypic variability in this progressive disease. The natural history of TTR amyloidosis, and treatments employed to manage it, are recorded in the global THAOS patient registry.

Design/Methods DESIGN/METHODS: Symptomatic patients with an amyloidogenic TTR mutation were categorized according to one of three phenotypes: cardiac (patients with heart failure, dyspnea, or cardiac rhythm disturbance, with minimal or absent neurologic or gastrointestinal symptoms); neurologic (those with neurologic symptoms, including walking disability, or gastrointestinal symptoms of any severity, who do not meet the cardiac phenotype criteria); or mixed (those not meeting either cardiac or neurologic phenotype criteria).

Results RESULTS: 556, 105, and 229 patients in the registry met criteria for neurologic, cardiac, or mixed phenotypes, respectively. Mean (±SD) age at disease onset was 39.8±13.5, 55.8±14.9, and 48.1±15.3 years, respectively. 82.6% of patients with a neurologic phenotype had the Val30Met mutation, with Phe64Leu, Glu89Gln, Ser77Tyr, and Ser50Arg mutations each represented by <3% of patients. A wider distribution of genotypes was reported for patients with the cardiac (Val122Ile, 30.5%; Val30Met, 28.6%; Ile68Leu, 6.7%; Leu111Met, 5.7%; Thr60Ala, 4.8%) and mixed (Val30Met, 59.8%; Val122Ile, 7.9%; Thr60Ala, 4.8%; Glu89Gln, 3.5%; Ile107Val, 2.6%) phenotypes. Mortality rate was lowest for the neurologic phenotype (3.9 per 100 patient-years); rates for cardiac and mixed phenotypes were similar (15.2 and 15.0 per 100 patient-years, respectively).

Conclusions CONCLUSIONS: The large collection of data from the THAOS registry is representative of TTR amyloidosis and provides a unique opportunity to refine the portrait of this heterogeneous disease along with its genotypic spectrum.

Authors/Disclosures
Violaine Plante-Bordeneuve, MD (CHU Henri Mondor) PRESENTER	Dr. Plante-Bordeneuve has nothing to disclose.
Teresa Coelho, MD (Unidate Clinica de Paramoloidose Hospital)	Dr. Coelho has nothing to disclose.
Victoria Lawson, MD, FAAN (Department of Neurology, Dartmouth-Hitchcock Medical Center)	Dr. Lawson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi.
Jennifer Schumacher, PhD (Pfizer)	No disclosure on file
	No disclosure on file
	No disclosure on file
Tanja D. Kuhlmann, MD	No disclosure on file
	No disclosure on file

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