title: Clinical presentations and skin denervation in amyloid neuropathy due to transthyretin Ala97Ser.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: N C-C
authors.initials: NC
authors.lastname: Yang
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lee
authors.forename: C-C
authors.initials: CC
authors.lastname: Chao
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chuang
authors.forename: W-M
authors.initials: WM
authors.lastname: Lin
authors.forename: M-F
authors.initials: MF
authors.lastname: Chang
authors.forename: P-C
authors.initials: PC
authors.lastname: Hsieh
authors.forename: H-W
authors.initials: HW
authors.lastname: Kan
authors.forename: Y-H
authors.initials: YH
authors.lastname: Lin
authors.forename: C-C
authors.initials: CC
authors.lastname: Yang
authors.forename: M-J
authors.initials: MJ
authors.lastname: Chiu
authors.forename: H-H
authors.initials: HH
authors.lastname: Liou
authors.forename: S-T
authors.initials: ST
authors.lastname: Hsieh
mesh_terms: D000368:Aged; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D017772:Amyloid Neuropathies / Q000175:diagnosis / Q000235:genetics; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D011228:Prealbumin / Q000235:genetics*; D012694:Serine / Q000235:genetics; D012867:Skin / Q000294:innervation* / Q000473:pathology
chemical_list: D011228:Prealbumin; D012694:Serine; D000409:Alanine