Transthyretin-Related Amyloidosis Differential Diagnoses

Updated: Jul 19, 2022
  • Author: Jefferson R Roberts, MD; Chief Editor: Emmanuel C Besa, MD  more...
  • Print

Diagnostic Considerations

Given the rarity of TTR-related amyloidosis (ATTR) and the challenge posed by its pattern of producing seemingly unrelated symptoms, ATTR has been widely underdiagnosed and misdiagnosed, thereby prolonging the time to appropriate treatment. Common misdiagnoses made in patients with peripheral nervous complaints include the following [22] :

  • Idiopathic axonal polyneuropathy
  • Chronic inflammatory demyelinating polyneuropathy
  • Lumbar spinal stenosis
  • Charcot-Marie-Tooth disease

With the high prevalence of alcoholism/alcohol abuse and diabetes in the United States population, neurologic findings may well be discounted as progressive sequalae of those known conditions, if present in an individual patient's history, and ATTR may be missed without further diagnostic workup.

The American Journal of Cardiology emphasizes the need for high degree of suspicion for ATTR in patients found to have heart failure with preserved ejection fraction along with symptoms related to the peripheral or autonomic nervous systems—information which patients may not offer unless the clinician specifically asks, in the course of a thorough interview focusing on signs, symptoms, and a complete family history. [25] Similarly, given the strong co-occurrence of cardiac and neurologic manifestations of ATTR, all patients with amyloid peripheral or autonomic neuropathy need screening for cardiac involvement.  

Differential Diagnoses