A description of variant transthyretin amyloidosis (ATTRv) stage 1 patients and asymptomatic carriers in Spain: the EMPATIa study.

Background: Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain.

Methods: National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected.

Results: The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group.

Conclusions: The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.