Weight loss in Huntington disease increases with higher CAG repeat number.
Neurology. 2008-11-03; 71(19): 1506-1513
DOI: 10.1212/01.wnl.0000334276.09729.0e
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1. Neurology. 2008 Nov 4;71(19):1506-13. doi: 10.1212/01.wnl.0000334276.09729.0e.
Weight loss in Huntington disease increases with higher CAG repeat number.
Aziz NA(1), van der Burg JM, Landwehrmeyer GB, Brundin P, Stijnen T; EHDI Study
Group, Roos RA.
Collaborators: Zangerl A, Seppi K, Wenning G, Poewe W, Foeldy D, Auff E, Schober
T, Wenzel K, Ott E, Walli J, Leblhuber F, Dürr A, Bloch F, Messouak O, Tallaksen
C, Dubois B, Guillamo JS, Bachoud-Lévi AC, Engles A, Krystkowiak P, Destée A,
Memin A, Thibaut-Tanchou S, Pasquier F, Azulay JP, Demonet JF, Galitzky M, Rascol
O, Mollion H, Broussolle E, Madigand M, Lallement F, Goizet C, Tison F,
Arguillère S, Viallet F, Bakchine S, Khoris J, Pages M, Camu W, Resch F,
Hannequin D, Durif F, Saudeau D, Autret A, Andrich J, Saft C, Kraus PH, Przuntek
H, Ecker D, Kramer B, Landwehrmeyer GB, Ludolph AC, Priller J, Meierkord H,
Kuznik D, Dose M, Squitieri F, Albanese A, Abbruzzese G, Filla A, van de
Warrenburg B, de Jong D, Kremer H, van Vugt J, Grimbergen Y, Roos R, Gawel M,
Janik P, Kowalczys H, Pilczuk B, Kwiecinski H, Swiat M, Ochudło S, Modestowicz R,
Niezgoda A, Łukasik M, Garcia de Yébenes J, García-Ruiz P, Martínez Descals A,
Rojo A, Fontán A, Hernández J, Cantarero S, Fanjul S, Alegre J, Giménez Roldán S,
Mateo D, Burguera JA, Solis P, Calopa M, Jaumà S, Bas J, Tolosa E, Muñoz JE,
Gámez J, Cervera C, Zarranz JJ, Lezcano E, Gómez JC, Chacón J, Dinca L, Gamero
MA, Redondo L, Castro A, Sesar A, López del Val J, López E, Ríos C, Castillio V,
Burgunder JM, Nirkko A, Kälin A, Vingerhoets F, Wider C.
Author information:
(1)Leiden University Medical Center, Department of Neurology, Leiden, The
Netherlands.
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.
DOI: 10.1212/01.wnl.0000334276.09729.0e
PMID: 18981372 [Indexed for MEDLINE]