Syncope, Urinary Retention, and Neuropathy in a 40-Year-Old

Amanda Kennedy, MD, MPH; Jeffrey Kaplan, MD; Dianna Quan, MD


February 27, 2023

Because most transthyretin is produced in the liver, liver transplantation has long been a mainstay of ATTRv amyloidosis treatment. Approximately 95% of the ATTRv production can be removed.[6,12] This can slow or halt, but does not reverse, the progression of neuropathy. Cardiac disease can also progress and may be due to deposition of wild-type ATTR produced by the transplanted liver. One study showed a trend toward improved survival with cardiac and liver transplant versus liver transplant alone; however, this result was not significant.[12]

Two TTR tetramer-stabilizing medications, tafamidis and diflunisal (a nonsteroidal anti-inflammatory drug), are available. By stabilizing the native tetramer form, the number of monomers available to form amyloid fibrils is reduced. This can slow progression of amyloid deposition but does not stop or reverse existing damage.[11] Tafamidis is currently approved in the United States for treatment of cardiomyopathy due to hereditary or wild-type ATTR amyloidosis.[13] The combination of doxycycline and tauroursodeoxycholic acid has been shown to reduce deposition of ATTR, which may help slow both cardiomyopathy and neuropathy.[11]

New therapies specifically approved in the United States for ATTRv amyloidosis with polyneuropathy include patisiran and inotersen. Patisiran is a small interfering RNA (siRNA) agent that reduces TTR synthesis via mRNA interference.[14] Inotersen is an antisense oligonucleotide that inhibits hepatic production of transthyretin. Both medications are taken into hepatocytes to reduce production of TTR and thereby deposition of ATTRv.[15]

The patient described in this case was initially started on diflunisal for treatment but continued to have progression of his neuropathy and autonomic symptoms. Owing to poor nutritional and hydration status, he required multiple hospital admissions and placement of a gastric tube. Biopsy of the duodenum, stomach, and colon showed ATTRv by mass spectrometry analysis (Figure 1).

Figure 1.

Cardiac MRI showed evidence of amyloid deposition, but the patient has had minimal cardiac dysfunction. Ophthalmologic evaluation revealed evidence of amyloid deposition in the vitreous; he ultimately had bilateral vitrectomies because of obscured vision. He was evaluated by the hepatology department and initially placed on the liver transplant list; however, owing to treatment and stabilization on siRNA therapy, he was ultimately taken off of the transplant list.


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