A new study found a wide range of initial features of hereditary transthyretin amyloidosis (hATTR), as well as disease risk and age of onset, among different families and geographic regions. The research, published in Amyloid, studied families from Sweden, Italy, Spain, France, Turkey, and Brazil.

“In hereditary transthyretin amyloidosis, early manifestation and age at onset (AO) may vary strikingly. We assessed the disease risk (penetrance), AO, and initial features in [hATTR] families to gain insights on the early disease presentation,” the authors wrote.

hATTR is an inherited, progressive disease that involves the accumulation of abnormally folded amyloid protein in various organs and organ systems. The heart, eyes, kidneys, gastrointestinal tract, and peripheral nervous system are particularly affected.

The disease is caused by mutations in the transthyretin (TTR) gene that encodes the TTR protein, which is produced in the liver. It is inherited in an autosomal dominant manner, meaning only 1 affected parent is required to transmit hATTR to offspring. In rare cases, hATTR can be caused by de novo sporadic mutations.

Read more about hATTR epidemiology

In this study, the research team collected genealogical data and analyzed 258 TTR V30M kindreds and 84 patients carrying 6 additional variants. They employed a nonparametric survival method to calculate penetrance.

The earliest risk of disease was found in Portugal and Spain at 20 years of age. In France and Sweden, individuals aged 30 to 35 years had the earliest disease risk. Men were at a higher risk, as were carriers of maternal descent. Peripheral neuropathy symptoms were the most common initial manifestations. Approximately 25% of those individuals carrying TTR non-V30M variants had an initial cardiac phenotype, and about 33% had a mixed phenotype.

The authors hope that the data obtained in this study will improve the ability to achieve early diagnoses and treatment for this rare disease.


Planté-Bordeneuve V, Gorram F, Olsson M, et al. A multicentric study of the disease risks and first manifestations in hereditary transthyretin amyloidosis (ATTRv): insights for an earlier diagnosis. Amyloid. Published online February 21, 2023. doi:10.1080/13506129.2023.2178891