Amyloidosis and autonomic failure

Amyloidosis is a group of disorders characterized by deposition of insoluble and degradation-resistant misfolded protein within various tissues leading to progressive organ failure. Deposition of amyloid in the peripheral nervous system can cause peripheral neuropathy and autonomic neuropathy. The neuropathy phenotype is most commonly a painful, length-dependent sensorimotor peripheral neuropathy but may vary based on amyloid types. Autonomic failure is usually a common predominant feature with orthostatic hypotension being the most frequent autonomic symptom. Amyloidosis is classified by the subunit of precursor protein comprising the amyloid fibrils and can be either acquired or hereditary. In this chapter, we review the two main subtypes of amyloidosis that affect the peripheral nerve, systemic light chain (AL) amyloidosis and hereditary transthyretin (TTR) amyloidosis, and discuss their clinical characteristics, diagnostic approach, disease prognosis, and updated therapeutic options.