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Science News: Variable Presentation of Hereditary Transthyretin-Mediated Amyloidosis at a Single Center

Submitted by: Shailesh Reddy, MD
Edited by: Sarah Chen, MD

Hussain Y. Variable presentation of hereditary transthyretin-mediated amyloidosis at a single center. J Clin Neuromuscul Dis. 2021;23(1):7-17. doi:10.1097/CND.0000000000000356

Summary: This is a retrospective study of 12 patients with a diagnosis of hereditary transthyretin-mediated (hATTR) amyloidosis at a single center in Austin, Texas. All patients were initially diagnosed with either polyneuropathy (83%) or myopathy (25%). These patients did not have cardiac symptoms at the time of presentation but 10 of them developed symptoms such as dyspnea and diastolic heart failure leading to a revision of their initial diagnosis. Eventually these patients were all diagnosed with haTTR amyloidosis by biopsy from various tissues (skeletal muscle, cardiac muscle, skin, and liver), nuclear scintigraphy, and genetic testing. Among them, 8 (67%) had cardiomyopathy-associated transthyretin mutations (V122I or T60A). The median time to diagnosis for these patients was 5 years (up to 10 years) during which their mobility had declined significantly. With the proper recognition of disease presenting symptoms and increased earlier screening or testing, hATTR amyloidosis could be diagnosed in a matter of months (in their center) and misdiagnosis can be avoided.
Comments: Although the sample size of this single-center study is quite small (N=12), it clearly demonstrated the diagnostic challenge. These patients had an average 5 years delayed time to their diagnosis of amyloidosis, mostly because typical “red flags” in the history were not present at time of their presentation. Amyloidosis is a rare etiology for peripheral neuropathy, however, it is often under recognized, causing a significant delay in diagnosis and misdiagnosis.
In addition, historically, polyneuropathy due to hATTR mutation is associated with V30M mutation. Cardiomyopathy symptoms have previously been associated with V122I variant. However in this study, in all cases patients had concurrent progressive polyneuropathy and cardiomyopathy, which suggests historical separation of two subtypes could be too rigid.
Timely diagnosis with accuracy and clarity is of utmost importance to neuromuscular medicine physicians, particularly with the rare and complex diseases like hATTR amyloidosis which has disease-specific therapies that could improve clinical outcomes.
This study drew awareness and vigilance of physicians of the range of symptoms and signs of hATTR amyloidosis that could expedite the diagnosis and treatment and also called for the collaboration of specialties to prevent diagnostic delay.
Article of Similar Interest:
Planté-Bordeneuve V, Ferreira A, Lalu T, et al. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP). Neurology. 2007;69(7):693-698. doi:10.1212/01.wnl.0000267338.45673.f4

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