Autonomic Dysfunction in Familial Amyloid Polyneuropathy Associated with Transthyretin Alanine 60 Variant (P5.105)
Bibliographic record
Abstract
Objective: We aimed to describe autonomic functioning in Thr60Ala carriers and healthy controls. Background:Familial Amyloid Polyneuropathy is an autosomal dominant disorder characterized in part by autonomic dysfunction. A specific subset results from a substitution of Alanine for Threonine at position 60 within the transthyretin gene (Thr60Ala). Methods: 11 carriers completed the Autonomic Reflex Screen. There was a significant age difference (p<0.001) between asymptomatic (n=6; 37±11 years) and symptomatic carriers (n=5; 62±14 years), requiring two age-matched control groups (n=12; 36±7 years; n=10; 62±6 years, respectively). Results:Sudomotor: There were no significant differences in the quantitative sudomotor axon reflex testing (QSART) sweat responses; all groups demonstrated normal sweat volumes. Cardiovagal: Symptomatic carriers had significantly reduced average HR differences during deep breathing (p<0.05) and significantly impaired Valsalva ratios compared to all other groups (p<0.001). When separated by age, older asymptomatic carriers demonstrated intact adrenergic functioning but a significantly reduced HR response to deep breathing compared to older controls (p=0.02). Adrenergic: Upon qualitative analysis of Valsalva, only symptomatic individuals demonstrated absent adrenergic phases. In addition, symptomatic carriers had the largest systolic BP drop during HUT, but mounted a significantly smaller compensatory tachycardia (p<0.05). Composite Autonomic Severity Score: Compared to all other groups, symptomatic carriers had significantly higher adrenergic and cardiovagal scores indicating greater impairment of these domains (p<0.001). There were no significant differences in sudomotor indices (p=0.3). Conclusions:Symptomatic carriers demonstrate cardiovagal and adrenergic dysfunction, but maintained post-ganglionic axon integrity. Compared to older controls, asymptomatic carriers showed significantly reduced HR responses to deep breathing beyond the normal aging effect. These data provide potential evidence of cardiovagal/cardiac impairment prior to adrenergic deficits. Given the importance of early detection we would argue that on-going surveillance and repeat autonomic testing for all carriers will provide better prognoses for Thr60Ala individuals.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".