Intracutaneous Amyloid Deposition is Associated With Nerve Conduction Studies Deterioration in Presumed Asymptomatic Pathogenic Variant TTR Carriers.

BACKGROUND

Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an autosomal dominant systemic disease, with an overall poor prognosis. Markers of disease onset are urgently required to optimize the timing of treatment initiation. Nerve conduction studies (NCS) are an objective, reproducible, and non-invasive tool for following large nerve fiber involvement. Our objective was to determine whether the presence of intracutaneous amyloid deposition (ICAD) was associated with a higher risk of developing the disease, defined as a decline observed on nerve conduction studies, in a population of carriers not meeting the criteria for overt disease.

METHODS

We included 98 presumed asymptomatic pathogenic variant TTR carriers with normal baseline NCS results and available follow-up testing results. Baseline evaluation included a neurological examination, short-term heart rate variability (HRV), electrochemical sweat conductance (ESC), intraepidermal nerve fiber density (IENFD), assessment of the presence of intracutaneous amyloid deposits (ICAD), and cardiac parameters. Follow-up neurological and cardiological evaluations were performed. NCS deterioration was defined as a 20% decrease in sensory nerve action potential (SNAP) in the lower limbs.

RESULTS

During a median follow-up of 5 years, 11/98 (11%) carriers presented a NCS deterioration. Presence of ICAD at baseline was significantly associated with NCS decline.

CONCLUSION

The presence of ICAD at baseline is associated with a subsequent NCS deterioration in presumed asymptomatic pathogenic variant TTR carriers. Skin biopsy for the analysis of amyloidosis deposit and small fiber density should be recommended in the evaluation of carriers and lead to discuss treatment initiation when abnormal, even in asymptomatic carriers.