Spectrum of hereditary transthyretin amyloidosis due to T60A(p.Thr80Ala) variant in an Irish Amyloidosis Network

Open Heart. 2024 Nov 11;11(2):e002906. doi: 10.1136/openhrt-2024-002906.

Abstract

Background: Variant transthyretin amyloidosis (ATTRv) is a hereditary multisystem disorder with clinical spectrum ranging from predominant cardiomyopathy to polyneuropathy. In the Irish population, the T60A mutation has been previously recognised as the most common genotype.

Objectives: The aim of this study is to describe the diagnostic and phenotypic spectrum of patients with T60A ATTRv attending an Irish Expert Amyloidosis Network.

Methods: In this observational study design, the medical, laboratory and radiological records of patients enrolled in our amyloidosis registry with a confirmed genotype diagnosis of T60A ATTRv were reviewed.

Results: A cohort of 24 patients (12 female) met criteria for inclusion. The median age at diagnosis was 65 years (IQR 59.5-66.5) and median follow-up 44 months (IQR 31-58). Carpal tunnel syndrome was the initial manifestation in almost half (46%) of patients. Overall, a mixed cardioneuro phenotype was demonstrated including autonomic (75%), small (58%) and large fibre (46%) neuropathy largely predating a cardiac phenotype consisting of heart failure (63%), atrial arrhythmia (42%) and bradycardia (13%).

Conclusion: The contemporary clinical spectrum of T60A ATTRv in Ireland is one of patients typically presenting in the seventh decade with an already manifest neuropathy phenotype, largely predating a cardiac phenotype dominated by heart failure.

Keywords: Cardiomyopathies; Heart Failure; Heart Failure, Diastolic.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Amyloid Neuropathies, Familial* / complications
  • Amyloid Neuropathies, Familial* / diagnosis
  • Amyloid Neuropathies, Familial* / epidemiology
  • Amyloid Neuropathies, Familial* / genetics
  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / genetics
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Humans
  • Ireland / epidemiology
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype*
  • Prealbumin* / genetics
  • Registries
  • Retrospective Studies

Substances

  • TTR protein, human
  • Prealbumin

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related