Objective: To systematically compare transthyretin with primary amyloid neuropathy to define their natural history and the underlying mechanisms for differences in phenotype and natural history. Methods: All patients with defined amyloid subtype and peripheral neuropathy who completed autonomic testing and electromyography at Mayo Clinic Rochester between 1993 and 2013 were included. Medical records were reviewed for time of onset of defined clinical features. The degree of autonomic impairment was quantified using the composite autonomic severity scale. Comparisons were made between acquired and inherited forms of amyloidosis. Results: One hundred one cases of amyloidosis with peripheral neuropathy were identified, 60 primary and 41 transthyretin. Twenty transthyretin cases were found to have Val30Met mutations; 21 had other mutations. Compared to primary cases, transthyretin cases had longer survival, longer time to diagnosis, higher composite autonomic severity scale scores, greater reduction of upper limb nerve conduction study amplitudes, more frequent occurrence of weakness, and later non-neuronal systemic involvement. Four systemic markers (cardiac involvement by echocardiogram, weight loss > 10 pounds, orthostatic intolerance, fatigue) in combination were highly predictive of poor survival in both groups. Interpretation: These findings suggest that transthyretin has earlier and greater predilection for neural involvement and more delayed systemic involvement. The degree and rate of systemic involvement is most closely related to prognosis. Ann Neurol 2016;80:401–411.
Bibliographical noteFunding Information:
This work was supported by the NIH NINDS (National Institute of Neurological Disorders and Stroke) (NS 44233, ?Pathogenesis and Diagnosis of Multiple System Atrophy? P.A.L.; U54 NS065736, ?Autonomic Rare Disease Clinical Consortium? P.A.L.; K23NS075141, ?Differential Approach to the Postural Tachycardia Syndrome?; W.S.), Mayo Center for Translational Science Activities (UL1 TR000135), and Mayo funds. The Autonomic Diseases Consortium is a part of the NIH Rare Diseases Clinical Research Network. Funding and/or programmatic support for this project has been provided by the NIH National Institute of Neurological Diseases and Stroke (U54 NS065736) and the NIH Office of Rare Diseases Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the NIH.
© 2016 American Neurological Association
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