title: A woman with a rare p.Glu74Gly transthyretin mutation presenting exclusively with a rapidly progressive neuropathy: a case report.
abstract: BACKGROUND
  Familial amyloid polyneuropathy is a rare autosomal dominant disorder caused by mutations in the transthyretin gene, TTR. Diagnosis can be challenging, especially if other family members are not affected or an obvious systemic involvement is lacking. The patients are often misdiagnosed, leading to a delay in the initiation of therapy.
  
  
  METHODS
  A 35-year-old woman of Turkish origin presented to our outpatient clinic with severe polyneuropathy associated with distally pronounced tetraparesis and hypesthesia of 2 to 3 years' duration. In addition, small nerve fiber involvement with impaired detection of cold temperatures and tingling pain in the lower legs was reported. She did not complain of autonomic dysfunction or visual disturbance. Her family history was empty regarding neuromuscular disorders. The routine diagnostic work-up was unremarkable. A sural nerve biopsy disclosed amyloid deposits, which led to the identification of a rare heterozygous transthyretin mutation (p.Glu74Gly; old classification: p.Glu54Gly).
  
  
  CONCLUSIONS
  Few cases with this very heterozygous mutation can be found in the literature. In contrast to the case of our patient, all of the previously described patients in the literature presented with additional severe autonomic symptoms, involvement of the eyes and a positive family history. In this case report, we emphasize that, in patients with progressive neuropathy with small fiber involvement, an amyloid neuropathy should be considered in the differential diagnosis, even if the family history is empty and other organs are not affected.
authors.affiliation: Institute of Neuropathology, Justus Liebig University, Arndstrasse 16, 35392 Giessen, Germany. anne.schaenzer@patho.med.uni-giessen.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Schänzer
authors.forename: Christoph
authors.initials: C
authors.lastname: Kimmich
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Thomas
authors.initials: T
authors.lastname: Haverkamp
authors.forename: Isabell
authors.initials: I
authors.lastname: Weidner
authors.forename: Till
authors.initials: T
authors.lastname: Acker
authors.forename: Heidrun H
authors.initials: HH
authors.lastname: Krämer
mesh_terms: D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D001583:Benzoxazoles / Q000627:therapeutic use*; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D008040:Genetic Linkage; D018698:Glutamic Acid; D005998:Glycine; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D020125:Mutation, Missense / Q000187:drug effects; D010375:Pedigree; D011228:Prealbumin / Q000187:drug effects / Q000235:genetics*
chemical_list: D001583:Benzoxazoles; D011228:Prealbumin; D018698:Glutamic Acid; C547076:tafamidis; D005998:Glycine