LAUSR

Introduction Familial transthyretin (TTR) amyloidosis is a rare disorder characterized primarily by progressive neuropathy and cardiomyopathy. The source of amyloid protein is the liver, thus early liver transplantation can significantly slow disease progression. Unfortunately, for some patients without significant cardiomyopathy at the time of transplant, cardiac disease can subsequently progress due to enhanced deposition of wild-type amyloid protein. Promising new medical therapies may soon replace liver transplant as the gold standard treatment. Case report A 67 year-old male with bilateral carpal tunnel syndrome presented with hematuria and was found to have bladder masses that stained positive for amyloidosis. A work-up for systemic amyloidosis included a normal bone marrow biopsy and an echocardiogram with LVH in the absence of increased voltage on ECG. Two years later he had a cardiac arrest in the setting of sustained VT. A left heart catheterization revealed normal coronary arteries. His endomyocardial biopsy Congo red stain was positive. He was diagnosed with a previously undiscovered mutation of familial TTR amyloidosis (Glu61Gly) and five years later underwent liver transplantation. He was NYHA Class I and did well for ten years before his functional capacity gradually declined. Serial echocardiograms showed a slow progression of LV wall thickness from 1.3 to 1.7 cm and a decline in LVEF from 50% to 30%. In addition, the defibrillation threshold of his ICD progressively increased. He underwent heart transplantation due to end stage amyloid cardiomyopathy. Postoperatively he developed ulcerative esophagitis and ultimately expired due to fungal pericarditis. Discussion Although liver transplantation can slow the progression of TTR amyloidosis and is an appropriate treatment for select individuals, new alternative medical therapies may replace early transplantation. Diflunisal, an anti-inflammatory drug, stabilizes the TTR tetramer in vitro and in a randomized trial slowed progression of neuropathy in familial TTR. Combined doxycycline and tauroursodeoxycholic acid disrupt TTR amyloid fibrils and appear to slow disease progression. Tafamadis, a small molecule that inhibits the dissociation of TTR tetramers has been shown in phase 2 and 3 trials to slow neuropathy progression and decrease mortality and heart failure hospitalizations. Patisiran is a small interfering RNA that blocks TTR synthesis and has demonstrated stabilization of neuropathy. Inotersen is an antisense oligonucleotide that has also shown promise in familial TTR patients with polyneuropathy. Most recently, an investigational monoclonal antibody has been designed to target and remove amyloid deposits. Conclusion Familial TTR amyloidosis is characterized by progressive neuropathy and cardiomyopathy for which patients may undergo liver transplant, though cardiac disease can subsequently progress. Promising new medical therapies may soon replace liver transplant as the gold standard.