title: Outcome of liver transplantation for familial amyloidotic polyneuropathy.
abstract: Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder caused by mutation in the transthyretin gene. The most common mutation is substitution of valine for methionine at position 30 (MET30). Liver transplantation (LT) is the preferred treatment. After LT, although many patients show stabilization or improvement in the disease, adverse outcomes have been reported in those who have malnutrition, long-standing disease, and non-MET (NMET) mutations at position 30. Our aim is to compare survival and outcome of symptoms associated with FAP after LT in patients with MET30 and NMET30 mutations. Medical records of all patients who underwent LT for amyloidosis at our institution were reviewed to obtain demographic information and clinical features, such as severity of neuropathy, diarrhea, orthostatic hypotension, and posterior wall or ventricle septal thickness before and after LT. Fifteen patients underwent LT for amyloidosis at our institution between 1990 and 2000 (MET30, n = 5; NMET30, n = 7; hereditary amyloidosis, n = 2; primary amyloidosis, AL type, n = 1). Patients with hereditary and primary amyloidosis were excluded from analysis. One- and 3-year survival rates after LT in MET30 patients were 100%. Before LT, five of five patients had sensorimotor neuropathy; five of five patients had diarrhea, and four of five patients had orthostatic hypotension. After LT, improvement or stabilization of neuropathy was seen in two of five patients; of diarrheal symptoms, in three of five patients; and of orthostatic hypotension, in three of four patients. One- and 3-year survival rates after LT in NMET30 patients were 100% and 85.7%, respectively. Before LT, six of seven patients had sensorimotor neuropathy, six of seven patients had diarrhea, and five of seven patients had orthostatic hypotension. After LT in this group, improvement or stabilization of neuropathy was seen in two of six patients; of diarrhea, in six of six patients; and of orthostatic hypotension, in five of five patients. Before LT, posterior wall and/or ventricle septal thickness was increased in two of five MET patients and seven of seven NMET patients. Five of seven NMET30 patients (71.4%) who received a combined liver and heart transplant had stabilization, and two patients in the NMET group and one patient in the MET group had progression of heart disease. Outcomes for LT for patients with FAP with MET or NMET mutations were similar. Earlier LT for patients with FAP with MET30 or NMET30 mutation would improve outcomes after LT.
authors: Division of Transplant Medicine, Mayo Clinic, Scottsdale, AZ, USA.
authors: Pratima
authors: P
authors: Sharma
authors: Roman E
authors: RE
authors: Perri
authors: Joseph E
authors: JE
authors: Sirven
authors: Steven R
authors: SR
authors: Zeldenrust
authors: David J
authors: DJ
authors: Brandhagen
authors: Charles B
authors: CB
authors: Rosen
authors: David D
authors: DD
authors: Douglas
authors: David C
authors: DC
authors: Mulligan
authors: Jorge
authors: J
authors: Rakela
authors: Russell H
authors: RH
authors: Wiesner
authors: Vijayan
authors: V
authors: Balan
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D003967:Diarrhea / Q000209:etiology / Q000235:genetics; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D016031:Liver Transplantation; D008239:Lysine / Q000235:genetics; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011228:Prealbumin / Q000235:genetics; D016896:Treatment Outcome; D014443:Tyrosine / Q000235:genetics; D014633:Valine / Q000235:genetics*
chemical_list: D011228:Prealbumin; D014443:Tyrosine; D008715:Methionine; D014633:Valine; D008239:Lysine; D000409:Alanine; D005998:Glycine