Familial amyloid polyneuropathy: When does it stop to be asymptomatic and need a treatment?
Transthyretin familial amyloid polyneuropathy (FAP) is a rare disease with autosomal transmission due to point mutation of the transthyretin (TTR) gene. It is the most disabling hereditary neuropathy affecting sensory, motor and autonomic nerves, and is irreversible and fatal within 7 to 12 years of onset in the absence of therapy. Diagnosis is usually delayed for 1-5 years because the onset is usually insidious, and a positive family history is lacking in 50% of late-onset cases. Penetrance is variable, and depends of the age of the carrier and age of onset in family members. Two treatments are available: liver transplantation, to suppress the main source of systemic production of mutant TTR; and TTR tetramer stabilizer drugs, to avoid the release of highly amyloidogenic monomers and oligomers. These therapies are able to stop or slow the progression of the disease in its early stages. Genetic counseling is crucial to detect carriers at risk of developing the disease. The European network for TTR-FAP recommends careful baseline assessment by questionnaire, clinical examination and neurophysiological tests, and periodic consultations to detect the onset of disease in time to start anti-amyloid therapy after biopsy findings of amyloid deposition. A therapeutic educational program is important for improving patients' awareness. Patients are considered symptomatic and ill when they themselves perceive symptoms or changes, including changes from baseline measurements on neurophysiological tests, followed by findings of amyloid deposition on biopsy. The most sensitive biopsies are from the labial salivary gland and skin.
Service de neurologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France; Inserm U1195, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. Electronic address: david.adams@aphp.fr.
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Adams
Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France; Unité de neurophysiologie clinique et épileptologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
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Beaudonnet
Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France; Service d'anatomopathologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Inserm U1195, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
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Adam
Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France; Service d'anatomopathologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Inserm U1195, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
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Lacroix
Service de neurologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France.
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Théaudin
Service de neurologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France.
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Cauquil
Service de neurologie, CHU Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Centre de référence national des neuropathies amyloïdes familiales et autres neuropathies périphériques rares (NNERF), 94275 Le Kremlin-Bicêtre cedex, France.
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Labeyrie
D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism
D011228:Prealbumin
Amyloidosis; Biopsy; Familial amyloid polyneuropathy; Neuropathy Impairment Score; Questionnaire; Small-fiber neuropathy; Symptomatic; Therapeutic educational program; Transthyretin