Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy

Neurology. 2004 Jul 13;63(1):129-38. doi: 10.1212/01.wnl.0000132966.36437.12.


Background: Late-onset type I familial amyloid polyneuropathy (FAP TTR Met30) cases unrelated to endemic foci in Japan show clinical features setting them apart from early-onset cases in endemic foci.

Objective: To compare pathologic features between the early- and late-onset types.

Methods: Pathologic findings in FAP TTR Met30 with onset before age 50 in relation to endemic foci (11 cases) were compared with those in 11 later-onset cases unrelated to endemic foci.

Results: Sural nerve biopsy specimens showed predominantly small-fiber loss in early-onset cases; variable fiber size distribution, axonal sprouting, and relatively preserved unmyelinated fibers characterized late-onset cases. Autopsy cases representing both groups showed amyloid deposition throughout the length of nerves and in sympathetic and sensory ganglia, but amounts were greater in early-onset cases. Amyloid deposition and neuronal cell loss were greater in sympathetic than dorsal root ganglia in early-onset cases; the opposite was true in late-onset cases. Size assessment of remaining neurons in these ganglia suggested predominant loss of small neurons in early-onset cases but loss of neurons of all sizes in late-onset cases. Transthyretin-positive, Congo red-negative amorphous material was more conspicuous in nerves from late- than early-onset cases. In extraneural sites, amyloid was more conspicuous in thyroid and kidney from early-onset cases and in heart and hypophysis from late-onset cases. In early-onset cases, cardiac amyloid deposition was prominent in the atrium and subendocardium but was conspicuous throughout the myocardium in late-onset cases.

Conclusion: The pathology of early- and late-onset FAP TTR Met30 correlated well with differences in clinical findings.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Substitution
  • Amyloid / analysis
  • Amyloid Neuropathies, Familial / classification
  • Amyloid Neuropathies, Familial / epidemiology
  • Amyloid Neuropathies, Familial / genetics
  • Amyloid Neuropathies, Familial / pathology*
  • Biopsy
  • Cell Count
  • Congo Red
  • Disease Progression
  • Ganglia, Sensory / pathology
  • Ganglia, Spinal / pathology
  • Ganglia, Sympathetic / pathology
  • Humans
  • Japan / epidemiology
  • Middle Aged
  • Mutation, Missense
  • Nerve Fibers / ultrastructure
  • Neurons / pathology
  • Prealbumin / genetics
  • Staining and Labeling
  • Sural Nerve / pathology
  • Viscera / chemistry
  • Viscera / pathology


  • Amyloid
  • Prealbumin
  • Congo Red