Volume 10 Supplement 1

First European Congress on Hereditary ATTR amyloidosis

Open Access

Unravelling the epidemiology of late-onset and asymptomatic carriers of FAP ATTR V30M in a Portuguese population

  • Carolina Lemos1,
  • Teresa Coelho2,
  • Miguel Alves-Ferreira1,
  • Diana Santos1,
  • Jorge Sequeiros1 and
  • Alda Sousa1
Orphanet Journal of Rare Diseases201510(Suppl 1):O3

https://doi.org/10.1186/1750-1172-10-S1-O3

Published: 2 November 2015

Background

Familial Amyloid Polyneuropathy (FAP ATTRV30M) is an AD systemic amyloidosis, due to a point mutation in the transthyretin (TTR) gene. Although in Portugal the disease has been characterized by its early onset (lower than 40yrs), a wider age-at-onset (AO) variability has been uncovered. The mean AO is 35.3, but more and more late-onset (higher than 50yrs) cases are being ascertained, often matched with older asymptomatic parents. Our aim now was to look into late-onset cases and aged-asymptomatic carriers in order to unravel familial aggregation of late-onset and to characterize these families regarding their epidemiology.

Methods

From the largest registry worldwide with 2754 patients (678 families), we analyzed a group of 326 late-onset cases (133 families) regarding gender and also their transmitting parent. Additionally we analyzed 222 asymptomatic carriers on regular follow-up, aged above 40 at last observation and their first-degree relatives, belonging to 122 families. We performed a descriptive analysis and used the Student's t-test for comparisons between groups.

Results

Age-at-onset was 60.03 for men and 59.25 for women (NS), as opposed to the general sample where women had a later onset (37.6) than men (33.4). Familial aggregation of late-onset cases is apparent, with some families having up to 11 late-onset cases. Out of 678 probands, ~40% had no affected parent at time of diagnosis, this figure being 86% (115/133) among late-onset probands. These parents had died with no signs of the disease mostly at old-age. No one had an affected parent with early-onset of the disease.

For asymptomatic carriers, age-at-last-observation varies between 40 and 49 for 103 subjects and was above 50 for 119 of them. Mean age-at-last-observation was 54.06 (SD: 12.2; range: 40-89) and no gender differences were found. We were able to identify 92 transmitting-parents (59 fathers, 33 mothers) with know AO. Their mean AO was 56.91 (SD: 12.8; range: 25-80) and no differences in AO were found between parent's gender. Also, we found a mean AO close to 40 years for siblings of these asymptomatic carriers (mean: 39.91; SD: 8.89; range: 24-65).

Conclusions

While most of FAP probands had one affected parent (as expected in an AD disease), a significant number has a late-onset and no affected parent at time of diagnosis. We confirmed familial aggregation of late-onset cases. We also found that for late-onset cases no gender differences are observed. This shows that some families are protected from the severe manifestations of FAP. Due to these different clinical aspects of FAP in late-onset patients it is crucial to explore mechanisms that can be related with aging and protective factors that can lead to new therapeutic strategies.

Authors’ Affiliations

(1)
IBMC and ICBAS, UnIGENe
(2)
Centro Hospitalar do Porto, Unidade Corino de Andrade

Copyright

© Lemos et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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