Neuropathic pain is a key early symptom of hereditary transthyretin amyloidosis (hATTR) and may be useful for monitoring disease progression, according to a study published in Frontiers in Neurology.

In hATTR, misfolded transthyretin (TTR) proteins accumulate in various parts of the body, including the peripheral nervous system. This can cause commonly reported symptoms such as feelings of pain described as electric shocks, pins and needles, and a burning sensation. Notably, many patients with early-onset hATTR report neuropathic pain among their first symptoms of the disease. 

The authors of this study sought to understand the nature of neuropathic pain in hATTR and how it impacts quality of life. They recruited adult participants who were carriers of known pathogenic TTR mutations, both symptomatic (n=78) and presymptomatic (n=24). Participants were only included if they did not have any comorbidities that could cause symptoms similar to neuropathic pain. 

The research team conducted a neurological examination on recruited participants and assessed their disease stage. In addition, they used scoring systems to evaluate the extent of neurological impairment and autonomic involvement, as well as overall disease impact on quality of life. If neuropathic pain was reported, the researchers recorded its distribution and severity. 

Read more about hATTR diagnosis

The results demonstrated that pain was reported in the participants overwhelmingly (75.5%). Specifically, neuropathic pain was described in 69.2% of symptomatic individuals and 8.3% of presymptomatic carriers. The presence of neuropathic pain was linked with greater pain severity and had a negative impact on activities of daily living. It was also significantly more common in participants with cardiomyopathy.

The presence of neuropathic pain in some individuals who were considered presymptomatic raises the question of whether they should be considered symptomatic and given access to treatment. Some scientists believe neuropathic pain is a clear symptom of hATTR, even in the absence of an instrumental demonstration of small nerve fiber impairment. 

“Assessment of neuropathic pain may be a useful strategy to monitor disease progression in symptomatic patients and may be suitable to identify early manifestation of the disease in presymptomatic relatives who carry a TTR gene mutation,” the authors of the study concluded.


Tozza S, Luigetti M, Antonini G, et al. Neuropathic pain experience in symptomatic and presymptomatic subjects carrying a transthyretin gene mutationFront Neurol. 2023;14:1109782. doi:10.3389/fneur.2023.1109782