BACKGROUND: Hereditary transthyretin amyloidosis (ATTR) is usually characterised 
by a progressive peripheral and autonomic neuropathy often with associated 
cardiac failure and is due to dominantly inherited transthyretin mutations 
causing accelerated amyloid deposition. The UK population is unique in that the 
majority of patients have the T60A missense mutation in ATTR where tyrosine is 
replaced by adenine at position 60. This has been traced to a single founder 
mutation from north-west Ireland. The neuropathy phenotype is less well 
described than the cardiac manifestations in this group.
METHODS: We present the findings from an observational cohort study of patients 
with ATTR attending the National Hospital Inherited Neuropathy Clinic between 
2009 and 2013. Detailed clinical neurological and electrophysiological data were 
collected on all patients alongside correlating autonomic and cardiac 
assessments. Follow-up data were available on a subset.
RESULTS: Forty-four patients with genetically confirmed ATTR were assessed; 37 
were symptomatic; mean age at onset=62 years, range=38-75 years; 75.7% male. 
T60A was the most common mutation (17/37), followed by V30M (5/37). A severe, 
rapidly progressive, predominantly length dependent axonal sensorimotor 
neuropathy was the predominant phenotype. T60A patients were distinguished by 
earlier and more frequent association with carpal tunnel syndrome; a 
predominance of negative sensory symptoms at onset; significant vibration 
deficits; and a non-length dependent progression of motor deficit. Progression 
of the neuropathy was observed over a relatively short follow-up period (2 
years) in 20 patients with evidence of clinically measurable annual change in 
Medical Research Council (MRC) sum score (-1.5 points per year) and Charcot 
Marie Tooth Neuropathy Score (CMTNS:2.7 points per year), and a congruent trend 
in the electrophysiological measures used.
CONCLUSION: The description of the ATTR neuropathy phenotype, especially in the 
T60A patients, should aid early diagnosis as well as contribute to the 
understanding of its natural history.