A Descriptive Analysis of ATTR Amyloidosis in Spain from the Transthyretin Amyloidosis Outcomes Survey

Abstract

Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene or aggregation of wild-type transthyretin (ATTRwt). In Spain, there are two large endemic foci of ATTR amyloidosis caused by the Val30Met variant, with additional cases across the country; however, these data may be incomplete, as there is no centralized patient registry. The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic patients with TTR mutations. This analysis aimed to gain a deeper understanding of the clinical profile of patients with ATTR amyloidosis in Spain.

Methods: This was a descriptive analysis of the demographic and clinical characteristics of symptomatic patients enrolled at six sites geographically dispersed throughout Spain (data cutoff: January 6, 2020). Patient data at enrollment, including genotype, demographics, and clinical presentation for symptomatic patients, were recorded. Patients were grouped by predominant phenotype based on clinical measures at enrollment: predominantly cardiac, predominantly neurologic, or mixed (cardiac and neurologic).

Results: There were 379 patients (58.0% male; 63.3% symptomatic) enrolled in the six THAOS sites in Spain. Predominant genotypes were the Val30Met mutation (69.1%) or ATTRwt (15.6%). Predominant phenotype distribution was neurologic (50.4%), mixed (35.8%), and cardiac (13.8%) for all symptomatic patients (n = 240); neurologic (67.8%), mixed (21.2%), and cardiac (11.0%) for symptomatic Val30Met (n = 146); and mixed (64.9%), cardiac (22.8%), and neurologic (12.3%) for symptomatic ATTRwt (n = 57). Symptomatic patients reported a range of ATTR amyloidosis signs and symptoms at enrollment, with autonomic neuropathy and sensory neuropathy common in all phenotypes.

Conclusions: These results from THAOS highlight the phenotypic heterogeneity associated with ATTR amyloidosis in Spain and the importance of comprehensive neurologic and cardiac evaluations in all patients with ATTR amyloidosis.

Trial registration: ClinicalTrials.gov: NCT00628745.

Keywords: Amyloidosis; Cardiac; Polyneuropathy; Spain; Transthyretin.

© 2021. The Author(s).

Figures

Fig. 1

Signs and symptoms at enrollment by predominant phenotype. Data cutoff: January 6, 2020. Cardiac phenotype, n = 33; neurologic phenotype, n = 121; mixed phenotype, n = 86. “Autonomic neuropathy” includes dizziness, dry eye, dyshidrosis, palpitations, recurrent urinary tract infections, urinary incontinence, urinary retention, vomiting, constipation, diarrhea, early satiety, fecal incontinence, nausea, erectile dysfunction. “Cardiac disorder” includes coronary artery disease, dyspnea, heart failure, other cardiovascular disease, rhythm disturbance, syncope, myocardial infarction. “Gastrointestinal” includes constipation, diarrhea, early satiety, fecal incontinence, nausea, unintentional weight loss, vomiting. “Motor neuropathy” includes muscle weakness, walking disability. “Other” includes adrenal insufficiency, cerebrovascular accident/stroke, cognitive decline, depression, dialysis, fractures, glaucoma, hyperlipidemia, inflammatory arthritis, inflammatory bowel disease, osteoarthritis, osteoporosis, other endocrine/metabolic disease, other eye disease, other gastrointestinal disease, other genitourinary/reproductive disease, other musculoskeletal disease, other neurologic diagnosis, other psychiatric diagnosis, other respiratory disease, pneumonia, renal impairment, thyroid dysfunction, visual impairment and vitrectomy, transplant, kidney stones, diabetes mellitus, asthma, chronic obstructive pulmonary disease, hepatitis, peptic ulcer disease, chronic demyelinating inflammatory polyneuropathy, carpal tunnel syndrome, seizures, schizophrenia. “Sensory neuropathy” includes balance abnormality, neuropathic arthropathy or pain/paresthesia, numbness, temperature/pain insensitivity, tingling. Categories are not mutually exclusive