Hereditary transthyretin cardiac amyloidosis proven by endomyocardial biopsy: a single-centre retrospective study and literature review

Abstract

Background

This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population.

Methods

Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed.

Results

TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54–69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis.

Conclusions

We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.

Keywords:

• Cardiac amyloidosis
• transthyretin
• hereditary
• endomyocardial biopsy

Acknowledgements

We would like to thank all of the participating families and investigators for their important contributions to this study. This research was supported by 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC18013).

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This research was supported by 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC18013).