Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe

Abstract

Purpose of reviewTransthyretin familial amyloid polyneuropathy (TTR-FAP) is a highly disabling, life-threatening disease characterized by progressive sensorimotor and autonomic neuropathy. The profile of the disease across Europe is inadequately understood at present.Recent findingsThe incidence and clinical presentation of TTR-FAP varies widely within Europe, with early and late-onset disease subtypes. In those regions in which the disease is endemic (Portugal, Sweden, Cyprus, and Majorca), a Val30Met substitution in the TTR gene is the predominant genetic cause, whereas in the rest of Europe, cases of TTR-FAP are mainly sporadic with genetic heterogeneity. Current management strategies lack cohesion and patients can experience years of misdiagnosis and suboptimal treatment.SummaryThe article aims to disseminate the findings and recommendations from two recent meetings of the European Network for TTR-FAP (ATTReuNET), a panel comprising representatives from 10 European countries (Bulgaria, Cyprus, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and Turkey) with expertise in the diagnosis and management of TTR-FAP. We explore the epidemiology and genetic mark of TTR-FAP across Europe and assess current management strategies, with a view to developing an alternative framework – a networked approach to disease management with an emphasis on collaboration and sharing of best practice.

Estimating the global prevalence of transthyretin familial amyloid polyneuropathy

“…The high estimate was derived as the summed prevalence from 2 population subgroups, Luso‐Brazilians and Portuguese non‐Luso‐Brazilians. ATTR‐FAP prevalence for Luso‐Brazilians was equal to the product of the subgroup population size (i.e., 25M15 and the prevalence rate given in Parman et al18 (i.e., 192.29/1M). ATTR‐FAP prevalence for Portuguese non‐Luso‐Brazilians was equal to the product of the subgroup population size (i.e., 182.8M16 and the mid prevalence rate applied elsewhere in this analysis (i.e., 1.48/1M18.…”

“…ATTR‐FAP prevalence for Luso‐Brazilians was equal to the product of the subgroup population size (i.e., 25M15 and the prevalence rate given in Parman et al18 (i.e., 192.29/1M). ATTR‐FAP prevalence for Portuguese non‐Luso‐Brazilians was equal to the product of the subgroup population size (i.e., 182.8M16 and the mid prevalence rate applied elsewhere in this analysis (i.e., 1.48/1M18.bFor the United States, an estimate from Benson19 (1/100,000 for the Caucasian population) was used as the high value per author judgment and was only applied to the Caucasian population (i.e., 248.8M28)).…”

“…1). One of the 10 retained records, Parman et al .,18 was published while our research was ongoing and was included retroactively. The search was rerun to include the year 2016, but no additional relevant records were identified.…”

“…Among the 10 retained records, 8 records18, 21, 22, 23, 24, 25, 26, 27 directly reported 25 prevalence estimates pertaining to 11 countries (for pertinent details of the 10 retained records, see Table 1). National level prevalence estimates were reported for 10 of the countries, and these 10 constituted the core group of countries for which ATTR‐FAP population sizes were directly estimable.…”

“…These values were derived from Parman et al .,18 which was a survey of ATTR‐FAP clinician and epidemiologist members of the European Network for ATTR‐FAP and reported the total number of known persons with ATTR‐FAP in their respective countries in the year 2014. Those values were combined with general population sizes to derive prevalence per 1 million general population.…”