Phenotypes of Late-Onset Transthyretin Amyloid Neuropathy: A Diagnostic Challenge

Abstract

Hereditary transthyretin amyloidosis (hATTR) is a rare cause of severe neuropathy, typically with progressive sensorimotor and autonomic manifestations. The clinical course is marked by progressive worsening with typical survival of 7–11 years following the onset of symptoms. The phenotype may resemble other types of neuropathy, and dysautonomia may be absent at onset delaying the diagnosis. Two medications were recently approved for treatment of hATTR neuropathy in the United States and more may follow. Three major phenotypes of hATTR include neuropathic, cardiac, and mixed. Diagnostic clues include “red-flag” symptoms reflecting typical multisystem involvement, often presenting with cardiomyopathy, gastrointestinal dysmotility, or kidney insufficiency. We present a case series of 4 patients with late-onset hATTR neuropathy who were initially diagnosed with vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy to illustrate diagnostic challenges encountered with hATTR. Early diagnosis is even more urgent now given the availability of disease modifying treatments.

hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

“…The sensitivity of abdominal subcutaneous fat aspiration is approximately 50%, while a biopsy of salivary glands has a reported sensitivity in expert hands of 75-90% [13,14]. Conversely, nerve biopsy is usually considered a second-line investigation, and it can reach a sensitivity cited as high as 80% [15][16][17][18]. However, negative biopsies in hATTR remain a frequent cause of diagnostic delay [4,15].…”

Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation

“…7,8 Only a few cases of ATTR upper limb predominant neuropathy and mononeuropathy multiplex have been reported. [9][10][11][12][13] In V122I-related familial transthyretin-related amyloidosis, carpal tunnel syndrome is common, 4 but upper limb predominant mononeuritis multiplex is a rarity. 9,12 In our patient, ATTR neuropathy was suspected after he was diagnosed with V122I-related ATTR cardiomyopathy and after exclusion of more common etiologies, such as infection, autoimmune disease, and vasculitis.…”