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


CONCLUSIONS
The pathology of early- and late-onset FAP TTR Met30 correlated well with differences in clinical findings.
Koike
H
H
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Misu
K
K
Sugiura
M
M
Iijima
M
M
Mori
K
K
Yamamoto
M
M
Hattori
N
N
Mukai
E
E
Ando
Y
Y
Ikeda
S
S
Sobue
G
G
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D000682:Amyloid / Q000032:analysis; D028227:Amyloid Neuropathies, Familial / Q000145:classification / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D001706:Biopsy; D002452:Cell Count; D003224:Congo Red; D018450:Disease Progression; D017950:Ganglia, Sensory / Q000473:pathology; D005727:Ganglia, Spinal / Q000473:pathology; D005728:Ganglia, Sympathetic / Q000473:pathology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D020125:Mutation, Missense; D009412:Nerve Fibers / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology; D011228:Prealbumin / Q000235:genetics; D013194:Staining and Labeling; D013497:Sural Nerve / Q000473:pathology; D014781:Viscera / Q000737:chemistry / Q000473:pathology
D000682:Amyloid; D011228:Prealbumin; D003224:Congo Red