In collaboration with Dr. Violaine Plant-Bordeneuve from the CHU of Bicêtre, Paris, we recently studied the penetrance of the disease, which determines the age of onset of the cases. Data of 623 patients were recorded (some followed at the CEPARM, others obtained only from family information), and the blood of individuals from 22 families was collected for genetic study. Our work showed that the penetrance at 60 years is 83%, i.e., in this age about 80% of the patients who present with the mutation will have already manifested the disease, especially between 30 and 35 years. The results also suggested a distinct origin of the mutations found in both the Portuguese/Brazilian and the Swedish populations. It is notheworthy that the first case which originated the disease in the Brazilian families probably occurred 650 years ago, preceding the Brazil’s discovery by the Portuguese, and thus taking place in Portugal. There is no doubt that our form of the disease is very much alike to the Portuguese one and originated from there.
If one considers that: (1) Rio de Janeiro is the “Portuguese” largest city outside Portugal; (2) the number of Luso-Brazilians descendants from the 1.5 million portuguese people who landed in Brazil after 1850 is estimated at 25 million, not including others that have come since the beginning of colonization; (3) and that these immigrants predominantly came from the north of Portugal, it will not be difficult to understand why the disease is significantly present in Brazil, especially in the southeast. Nevertheless it has frequently been underdiagnosed, especially those cases not manifesting the most common disease pattern and presenting a later onset, absence of family history or particular characteristics.
It is important to note that the complete sequencing of the transthyretin (TTR) gene has been performed for genetic diagnosis for some years. This method of DNA analysis allows us to detect not only the most common TTR mutation found in both world and Brazilian populations (Val30Met), but also any other mutation that can occur in this gene. In this way, we have already detected several cases presenting other mutations different from val30met, said “not val30met”, that sometimes determine the development of atypical neurological manifestations, leading, e.g., to cardiomyopathy. In these cases, patients often remain without a diagnosis, as well as a proper treatment, for years, being found in cardiology services, among others.
The CEPARM aims to aware the Brazilian and Latin-American medical communities (specially neurologists, but also cardiologists and other clinicians) to the frequent underdiagnosis of this condition, either because of the diagnostic difficulty itself or due to atypical presentation, thus aiding earlier diagnosis of the disease and a more effective treatment.