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

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.