Autonomic involvement in hereditary transthyretin amyloidosis (hATTR amyloidosis).

PURPOSE: Hereditary transthyretin amyloidosis (hATTR amyloidosis) is a progressive disease primarily characterized by adult-onset sensory, motor, and autonomic neuropathy. In this article, we discuss the pathophysiology and principal findings of autonomic neuropathy in hATTR amyloidosis, the most common methods of assessment and progression, and its relation as a predictive risk factor or a measure of progression in the natural history of the disease.

METHODS: A literature search was performed using the terms "autonomic neuropathy," "dysautonomia," and "autonomic symptoms" in patients with hereditary transthyretin amyloidosis and familial amyloid polyneuropathy.

RESULTS: Various scales to measure autonomic function have been employed, particularly within the major clinical trials, to assess novel therapies for the disease. Most of the evaluations were taken from diabetic clinical trials. Questionnaires include the COMPASS-31 and Norfolk QOL autonomic nerve function domain, whereas clinical evaluations comprise HRDB and the orthostatic tolerance test. Several treatment options are being employed although only diflunisal and tafamidis have reported improvement in the autonomic abnormalities.

CONCLUSIONS: Autonomic nerves are often affected before motor nerve impairment, and dysautonomia may support the diagnosis of hATTR amyloidosis when differentiating from other adult-onset progressive neuropathies and from other types of amyloidosis. Most of the progression of autonomic dysfunction is seen in early stages of the disease, commonly before motor impairment or affection of the overall quality of life. Unfortunately, there is no current single standardized approach to evaluate dysautonomia in hATTR amyloidosis.