Yang N.C.-C.Lee M.-J.CHI-CHAO CHAOChuang Y.-T.Lin W.-M.Kan H.-W.PAUL-CHEN HSIEHMING-FONG CHANGLin Y.-H.CHIH-CHAO YANGMING-JANG CHIUHORNG-HUEI LIOUSUNG-TSANG HSIEH2020-11-032020-11-032010-08-100028-3878https://www.scopus.com/inward/record.uri?eid=2-s2.0-77955442857&doi=10.1212%2fWNL.0b013e3181ec7fda&partnerID=40&md5=621a5d95cf696726f69d27105661ab0ahttps://scholars.lib.ntu.edu.tw/handle/123456789/519938Objective: Familial amyloid polyneuropathy (FAP) due to amyloidogenic transthyretin (TTR) is often associated with impairment of thermonociceptive functions. This study investigated skin innervation and its clinical significance in genetically defined FAP due to a hot-spot Ala97Ser TTR mutation (Ala97Ser). Methods: Skin biopsies were performed on the distal leg of patients with Ala97Ser, and intraepidermal nerve fiber (IENF) densities were quantified. Results: There were 19 unrelated patients with Ala97Ser manifesting a late-onset (59.47 ± 5.70 years) generalized neuropathy with disabling motor, sensory, and autonomic symptoms. Against a background of a slowly progressive course, 7 patients (36.8%) exhibited additional rapid declines in neurologic deficits, which were associated with elevation of the protein content in the CSF (p < 0.001). The IENF density was markedly reduced in Ala97Ser patients compared to age-and gender-matched controls (0.99 ± 1.11 vs 8.31 ± 2.87 fibers/mm, p < 0.001). Skin denervation was present in all patients and was lower in patients with a higher disability grade (0.17 ± 0.26 vs 1.37 ± 1.16 fibers/mm, p = 0.003). Albuminocytologic dissociation in the CSF was observed in 14 patients (73.7%), and the IENF density was negatively correlated with the CSF protein concentration (p = 0.015). Conclusions: Skin denervation was common in Ala97Ser, and degeneration of cutaneous nerve terminals was correlated with the severity of clinical phenotypes and the level of CSF protein. ? 2010 by AAN Enterprises, Inc. All rights reserved.en[SDGs]SDG3alanine; prealbumin; serine; alanine; prealbumin; serine; adult; aged; article; autonomic dysfunction; cerebrospinal fluid; clinical article; clinical feature; comparative study; control group; controlled study; denervation; disease course; familial amyloid polyneuropathy; female; gene mutation; human; human tissue; male; motor dysfunction; nerve fiber; neurologic disease; phenotype; priority journal; restriction fragment length polymorphism; sensory dysfunction; skin biopsy; skin denervation; amino acid substitution; Amyloid Neuropathies; Amyloid Neuropathies, Familial; genetics; innervation; middle aged; missense mutation; pathology; skin; Aged; Alanine; Amino Acid Substitution; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Female; Humans; Male; Middle Aged; Mutation, Missense; Prealbumin; Serine; Skin; Aged; Alanine; Amino Acid Substitution; Amyloid Neuropathies; Amyloid Neuropathies, Familial; Female; Humans; Male; Middle Aged; Mutation, Missense; Prealbumin; Serine; Skinjournal article10.1212/WNL.0b013e3181ec7fda206971052-s2.0-77955442857