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Weight loss in Huntington disease increases with higher CAG repeat number

N A Aziz1, J M M van der Burg, G B Landwehrmeyer

  • 1Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands. N.A.Aziz@lumc.nl

Neurology
|November 5, 2008
PubMed

Insights

Weight loss in Huntington disease (HD) is linked to CAG repeat length, not other symptoms. This suggests a hypermetabolic state may cause weight loss in HD patients.

Area of Science:

  • Neuroscience
  • Genetics
  • Metabolism

Background:

  • Huntington disease (HD) is an inherited neurodegenerative disorder.
  • Weight loss is a common but poorly understood symptom of HD.

Purpose of the Study:

  • To investigate the mechanisms behind weight loss in HD.
  • To determine the relationship between weight loss and disease characteristics, including CAG repeat length.

Main Methods:

  • Analyzed weight changes over 3 years in 517 early-stage HD patients using mixed-effects models.
  • Correlated weight changes with CAG repeat number and Unified Huntington's Disease Rating Scale (UHDRS) scores.
  • Examined CAG repeat length, body weight, and caloric intake in the R6/2 mouse model of HD.

Main Results:

  • Mean body mass index decreased by 0.15 units per year in HD patients.
  • No specific motor, cognitive, or behavioral UHDRS component independently predicted weight loss.
  • Higher CAG repeat length correlated with faster weight loss in patients and lower body weight in mice.
  • Caloric intake increased with longer CAG repeat length in the mouse model.

Conclusions:

  • Weight loss in HD is directly associated with CAG repeat length.
  • A hypermetabolic state is the likely cause of weight loss in early HD.
  • Other HD symptoms are unlikely to drive weight loss in early stages.
  • Understanding these mechanisms may enable the development of energy-based therapies for HD.
Abstract

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