Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016.
Department of Transplant Medicine, University Hospital Münster, Münster, Germany.
Hartmut H-J
HH
Schmidt
Department of Neurology, Institute for Neurological Research Raúl Carrea, FLENI, Buenos Aires, Argentina.
Fabio
F
Barroso
Department of Neurology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Alejandra
A
González-Duarte
Department of Neurology, Centro Hospitalar Norte-Hospital de Santa Maria, Lisbon, Portugal.|Translational and Clinical Physiology Unit, Institute of Molecular Medicine, Faculty of Medicine, Lisbon, Portugal.
Isabel
I
Conceição
Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Laura
L
Obici
Pfizer, Inc., New York, New York, USA.
Denis
D
Keohane
Pfizer, Inc., New York, New York, USA.
Leslie
L
Amass
D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D019468:Disease Management; D006801:Humans; D011228:Prealbumin / Q000235:genetics*
D011228:Prealbumin
amyloidosis; carrier; familial amyloid polyneuropathy; predictive genetic testing; transthyretin