title: "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy.
abstract: Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, progressive, life-threatening, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin-derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR-FAP is frequently diagnosed late because the disease is difficult to recognize due to phenotypic heterogeneity. Based on published literature and expert opinion, symptom clusters suggesting TTR-FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. TTR-FAP should be suspected if progressive peripheral sensory-motor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR-FAP is suspected, transthyretin genotyping, confirmation of amyloid in tissue biopsy, large- and small-fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed.
authors.affiliation: CHLN - Hospital de Santa Maria, and Clinical and Translational Physiology Unit, Faculty of Medicine-IMM, Physiology Institute, Lisbon, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Conceição
authors.affiliation: Department of Neurology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: González-Duarte
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.affiliation: Klinik für Transplantationsmedizin, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Hartmut H-J
authors.initials: HH
authors.lastname: Schmidt
authors.affiliation: Medical Division, Pfizer International Operations, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Simoneau
authors.affiliation: Global Medical Affairs, Global Innovative Pharma, Pfizer Inc, New York, NY, USA.
authors.forename: Moh-Lim
authors.initials: ML
authors.lastname: Ong
authors.affiliation: Global Medical Affairs, Global Innovative Pharma, Pfizer Inc, New York, NY, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Amass
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis*; D042241:Early Diagnosis; D006801:Humans
keywords: diagnosis; hereditary amyloidosis; transthyretin; transthyretin familial amyloid neuropathy