Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas.
OBJECTIVE
The objective of this study was to elucidate the natural history of late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) in non-endemic areas.


METHODS
The authors retrospectively assessed the development of major clinical landmarks and abnormalities of nerve conduction and cardiac examination indices in 50 patients with an age of onset older than 50 years and no relationship to endemic foci.


RESULTS
Once the neuropathic process was initiated, sensory and motor symptoms of both the upper and lower extremities appeared within a period of one and a half years. Digestive and orthostatic symptoms also tended to occur in the early phase of the disease, whereas urinary symptoms appeared in the middle of the disease progress. Along with pain in the extremities, these symptoms progressed over time and significantly disturbed the quality of life during the late phase of the disease, resulting in the need for wheelchair use. Although cardiomyopathy became clinically apparent only in the late phase of the disease, it was found to be the major cause of death. The mean duration of the disease onset to death was 7.3 years. Although values at the time of diagnosis were extremely variable, serial measurements of electrophysiological indices, the cardiothoracic ratio and interventricular septum thickness indicated a steady exacerbation in these outcomes among patients within a span of a couple of years.


CONCLUSIONS
The ages of onset of each clinical landmark were extremely variable between patients. However, once an initial symptom appeared, the chronological sequence of other clinical landmarks tended to be uniform, occurring within a relatively short time span.
Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. koike-haruki@med.nagoya-u.ac.jp
Haruki
H
Koike
Fumiaki
F
Tanaka
Rina
R
Hashimoto
Minoru
M
Tomita
Yuichi
Y
Kawagashira
Masahiro
M
Iijima
Junko
J
Fujitake
Toru
T
Kawanami
Takeo
T
Kato
Masahiko
M
Yamamoto
Gen
G
Sobue
D000200:Action Potentials / Q000502:physiology; D017668:Age of Onset; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology; D002423:Cause of Death; D018450:Disease Progression; D019353:Endemic Diseases; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000209:etiology / Q000628:therapy; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000235:genetics / Q000503:physiopathology; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology; D009460:Neurologic Examination; D010138:Pacemaker, Artificial; D010146:Pain / Q000209:etiology; D011228:Prealbumin / Q000235:genetics*; D012189:Retrospective Studies; D012678:Sensation Disorders / Q000209:etiology; D014463:Ultrasonography
D000682:Amyloid; D011228:Prealbumin