P235: Hereditary Transthyretin-Related Amyloidosis Ongoing Clinical Study: A Baseline Report of the First 3,167 Participants

Poster Presenter

Pierre Engel

Senior Director Business Development
Centogene Gmbh
Germany

Objectives

The current study aims to dive deeper into the understanding of hATTR amyloidosis.

Method

In Germany, the observational prospective TRAMmoniTTR study on Hereditary Transthyretin-related Amyloidosis enrolled since 2020 up to 3167 patients followed up over a 24-month period. Next-gen sequencing was used to ascertain cases. Genotype phenotype relationships was also studied.

Results

Standard descriptive statistics were performed. The median age of the participants was 67 years (interquartile range 55-78), with a predominance of male individuals (66%). Over 50% of the participants were overweight or obese (BMI>25). We identified five main clinical phenotypes out of 22 single symptoms that explained 45% of the variation. The first two principal component analyses (PCA) referred to polyneuropathy and cardiomyopathy. We found significant differences between gender and the PCA polyneuropathy and PCA cardiomyopathy, with a male over-representation in the higher quantiles of PCA polyneuropathy, and male under-representation in the lowest quantiles of PCA cardiomyopathy. Furthermore, we identified 17 unique heterozygous TTR variants, most of them classified as pathogenic/likely pathogenic (3% of the participants), with p.Val50Met being the most frequent. Variant-specific analysis showed a borderline over-representation of heterozygotes for p.Val50Met with cardiomyopathy.

Conclusion

The TRAMmoniTTR study is the largest study to date in aTTR patients in Germany. Our findings are consistent with other large observational studies with a slightly higher proportion of patients. The broad range of symptoms observed in patients at the time of enrollment highlights the necessity of a multidisciplinary approach to managing all types of ATTR amyloidosis Longitudinal. Although we were able to new variants never observed in the literature, larger studies will be needed to better characterize TTR genetic-phenotype correlations. patients positive for P/LP variants.