Epidemiology of Transthyretin Familial Amyloid Polyneuropathy in Portugal: A Nationwide Study

Abstract

Background: Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a rare, hereditary, progressive and neurodegenerative disease. We aimed to study ­TTR-FAP epidemiology in Portugal. Methods: National, observational, prospective and retrospective, case identification of adults with TTR-FAP. Countrywide patient multiple identification sources included reference centers registries and centralized medical electronic prescription database. Crude rates were reported per 100,000 adult inhabitants. Results: Over 2010–2016 period, mean incidence rates was 0.87/100,000 (95% CI 0.68–1.10) corresponding to 71 new patients yearly, that has decreased 31% in the last 7 years. The proportion of late-onset cases (age ≥50 years) among incident cases was 28.7%. Estimated crude 2016 prevalence was 22.93/100,000 adult inhabitants (95% CI 21.90–23.99) corresponding to 1,865 TTR-FAP individuals in Portugal (45.8% male; mean age: 52.3 ± 15.4 years). In 2016, the Portuguese region with the highest TTR-FAP prevalence shows a 16% prevalence increase over the last 25 years. Conclusions: In Portugal, TTR-FAP affects both genders and mainly young adults. TTR-FAP incidence appears to be decreasing while prevalence is increasing. In comparison to previous studies, there is an increased representativeness of late-onset patients. This epidemiological setting poses future and complex challenges for the social and healthcare system, strengthening the relevance of regular epidemiologic surveillance.

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study

“…The proportion of male, age and educational attainment differed between groups (p < 0.001). As expected, median age was lower among asymptomatic carriers and patients, as the disease affects mainly young adulthood [3]. Asymptomatic carriers were mostly female, younger and with higher level of educational attainment, as compared with general population subjects and patients.…”

“…Hereditary transthyretin amyloid polyneuropathy (hATTR-PN) is a rare genetic disease, originally described in 1952 by Corino de Andrade in northern Portugal [1]. hATTR-PN is estimated to affect up to 10,000 people worldwide [2], the largest cohort of patient being Portuguese [3], almost all (> 99% families) carrying the Val30Met mutation [4]. The disease is related to mutations in the transthyretin (TTR) gene, leading to deposition of amyloid fibrils in the peripheral nerves and in vital organs [5].…”

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series

“…The relatively higher onset age reported here might also reflect changing trends in disease characteristics at presentation that have been influenced by better disease awareness and population factors such as decreasing fertility rates. In their recently published epidemiological assessment of ATTR-PN in Portugal, Ines et al (2018) implicated these same factors as likely reasons for a higher incident age [23]. The authors noted that the ratio of late-onset to early-onset incident cases nearly doubled from 1:4 (22.4%) to 2:4 (44.4%) between 2010 and 2016.…”

Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy

“…1 TTR-FAP is rare with endemic populations predominantly in Portugal, Sweden, Japan, and Brazil. [2][3][4] Its symptoms stem from amyloidosis that results from misfolding of the TTR protein tetramer. 2,[5][6][7] More than 120 TTR gene mutations are associated with TTR-FAP, the most common of which is Val30Met.…”