Abstract

Hereditary amyloidosis related to transthyretin (ATTR) is a rare and progressive disease that, despite the phenotypic heterogeneity, a length-dependent sensorimotor axonal neuropathy (ATTR-PN) is the classic hallmark. Timely diagnosis is paramount for early treatment implementation. Sixty-nine asymptomatic gene carriers (Val30Met) were assessed during a 4-year period to identify those remaining asymptomatic versus those converting to ATTRV30M-PN. Conversion to symptomatic was defined as presenting with two definite symptoms of ATTRV30M-PN. Composite neurophysiological scores of sensory (SNS), motor (MNS), and sympathetic skin response (SSRS) amplitudes were used to assess neuropathy progression. We used mixed-effects modeling and ordinal logistic regression to assess neurophysiological evolution over time. Of all asymptomatic gene carriers, 55.1% (n = 38/69) converted over the period of this analysis. The progression of the SNS relative to baseline was different between groups (asymptomatic gene carriers vs. converters), the decline being greater in the converter group (time × group interaction p = 0.040), starting about 2 years before symptom onset. No significant change occurred regarding MNS or SSRS. Moreover, the percentage of cases with an annual decline on the SNS of at least 25%, gradually and significantly increased in the converter group, representing a 1.92 increase in risk of developing symptoms for those with such reduction on the last evaluation. A simple composite neurophysiological sum score can predict the onset of ATTRV30M-PN symptoms by as much as 2 years, highlighting the importance of a systematic follow-up of asymptomatic gene carriers, allowing a timely diagnosis, and management of symptomatic disease.

Keywords

MeSH terms