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Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation |
Adriano-Valerio Schettini a , Laura Llado b , JulieK Heimbach c , JoseGonzalez Costello d , Marie Tranang e , Olivier Van Caenegem f , Richard C Daly g , Peter Van den Bergh h , Carlos Casasnovas i , Joan Fabregat b , John J Poterucha j , Maxime Foguenne a , Bo Göran Ericzon k , Jan Lerut a , ∗ |
a Institute for Experimental and Clinical Research (IREC), Catholic University of Louvain (UCL), Avenue Hippocrate 55, Brussels 1200, Belgium
b Liver Transplant Unit, Department of Surgery, Hospital Universitari de Bellvitge, Calle de la Feixa Llarga, Barcelona 08907, Spain
c Division of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA
d Advanced Heart Failure and Transplant Unit, Cardiology Department, Hospital Universitari de Bellvitge, Calle de la Feixa Llarga, Barcelona 08907, Spain
e Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR), Division of Transplantation Surgery, Karolinska Universitetssjukhuset Huddinge, F82, Karolinska Institutet, Stockholm 141 86, Sweden
f Cardiothoracic Intensive Care Unit, Department of Cardiovascular Diseases, University Hospitals Saint-Luc - UCL, Avenue Hippocrate 10, Brussels 1200, Belgium
g Cardiovascular Surgery Department, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA
h Neuromuscular Reference Centre, University Hospital Saint-Luc - UCL, Avenue Hippocrate 10, Brussels 1200, Belgium
i Neuromuscular Unit, Neurology Department, Hospital Universitari de Bellvitge, Calle de la Feixa Llarga, Barcelona 08907, Spain
j Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st St SW, Rochester MN 08907, USA
k Division of Transplantation Surgery, CLINTEC, Karolinska Universitetssjukhuset Huddinge, F82, Karolinska Institutet, Stockholm 14186, Sweden
∗ Corresponding author.
E-mail address: jan.lerut@uclouvain.be (J. Lerut). |
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Abstract Background: Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils (i.e. amyloid). Apart from the common Val30Met mutation there is a very heterogeneous group of non-Val30Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy.
Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed.
Results: Three patients needed a staged (1 patient) or simultaneous (2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac (allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months.
Conclusions: This is the first report in (liver) transplant literature about the rare Val122del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.
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