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Weight loss in Huntington disease increases with higher CAG repeat number

Aziz, N. A.; van der Burg, Jorien m LU ; Landwehrmeyer, G. B.; Brundin, Patrik LU ; Stijnen, T. and Roos, R. A. C. (2008) In Neurology 71(19). p.1506-1513
Abstract
Objective: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. Methods: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in... (More)
Objective: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. Methods: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD. Results: In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length. Conclusions: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics. Neurology (R) 2008;71:1506-1513 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurology
volume
71
issue
19
pages
1506 - 1513
publisher
American Academy of Neurology
external identifiers
  • wos:000260601500009
  • scopus:56149125562
ISSN
1526-632X
DOI
10.1212/01.wnl.0000334276.09729.0e
language
English
LU publication?
yes
id
bb0d0c31-a68d-4d92-bf90-a0c72222cf05 (old id 1283844)
date added to LUP
2009-02-09 11:07:52
date last changed
2017-11-19 03:54:19
@article{bb0d0c31-a68d-4d92-bf90-a0c72222cf05,
  abstract     = {Objective: Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number. Methods: In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD. Results: In patients with HD, mean body mass index decreased with -0.15 units per year (p &lt; 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length. Conclusions: Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics. Neurology (R) 2008;71:1506-1513},
  author       = {Aziz, N. A. and van der Burg, Jorien m and Landwehrmeyer, G. B. and Brundin, Patrik and Stijnen, T. and Roos, R. A. C.},
  issn         = {1526-632X},
  language     = {eng},
  number       = {19},
  pages        = {1506--1513},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Weight loss in Huntington disease increases with higher CAG repeat number},
  url          = {http://dx.doi.org/10.1212/01.wnl.0000334276.09729.0e},
  volume       = {71},
  year         = {2008},
}