Alternative names: familial amyloid polyneuropathy, transthyretin-related hereditary amyloidosis, hATTR, Andrade disease, doença dos pezinhos
Locus: TTR
OMIM: https://omim.org/entry/105210
This hereditary disease is unusual because it seems to originate from only a few places in the world.
In 2024, Per Roos and Sebastian Wärmländer of the Karolinska Institute in Stockholm, Sweden, remarked that the largest clusters of the disease have something in common: they are all located in or near ancient mining districts. They argue that this implies exposure to heavy metals may be one of its causes. If true, carriers of certain TTR mutations would be more likely to develop the disease when exposed to high levels of heavy metals. The authors do not specify which ones they think are the culprit.
We are now undertaking field trips to several geographical foci of hATTR across Europe, in order to investigate whether specific exposures in those areas are in line with their generalization. We are led to ask: if heavy metals do play a role in etiology, why not include exposure to metals of industrial and other sources in the model? This may improve its explanatory power. And are heavy metals the only relevant environmental exposure?
Roos and Wärmländer restrict their model to just one subtype of hATTR, associated with polyneuropathy. But what about geographical foci of the other major subtype of the disease, associated with cardiomyopathy? Do we find the same, or similar, environmental stressors there?
These are some of the empirical questions raised by the interesting proposal of these two Swedish authors. We believe it does have predictive power, but can be improved upon with additional ecological research.
References:
P. Roos and S. Wärmländer, 2024, Hereditary Transthyretin Amyloidosis (hATTR) with Polyneuropathy Clusters Are Located in Ancient Mining Districts: A Possible Geochemical Origin of the Disease. https://pubmed.ncbi.nlm.nih.gov/38927056/