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

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.