Weight loss in early stage of Huntington’s disease

Abstract

At an early stage of the disease, subjects with Huntington's disease had lower body mass index than matched controls from the general population. The cause of weight loss is unknown but the parallel to observations in Huntington's disease transgenic mice suggests that it is a significant hallmark of Huntington's disease gene expression.

Increased apoptosis, huntingtin inclusions and altered differentiation in muscle cell cultures from Huntington's disease subjects

“…As myoblasts are essential, in vivo, for normal growth, repair, and maintenance of adult skeletal muscle bulk, 18 an increased rate of cell death associated with impaired myotube formation may contribute to the progressive weight loss observed in patients with HD. 5 The increased apoptosis and muscle cell dysfunction are consistent with the severe muscular atrophy detected in transgenic HD mice 10 and accord with nonspecific myopathic Figure 3 Analysis of myoblast survival. HD (filled squares) and control (open squares) myoblast survival.…”

“…1 In patients, progressive widespread brain atrophy, 2,3 leading to severe motor disability over time, is associated with early peripheral tissue dysfunction such as loss of body weight. 4,5 Hence, the pathological involvement of non-nervous tissues may contribute to the clinical features of HD.…”

Sleep deficits but no metabolic deficits in premanifest Huntington's disease

“…Similarly, altered energy expenditure and balance have been shown in HD patients,17, 18, 19 and might underlie the progressive weight loss reported to occur early on in this condition 6, 20. This raises questions as to whether metabolic problems in HD also exist ahead of motor features and disease diagnosis and may occur at the same time as sleep and circadian problems, suggesting a common neuropathological substrate that may involve the hypothalamus 21…”

“…It is caused by an abnormal expansion of a trinucleotide cytosine–adenosine–guanosine repeat (CAG)3 in exon 1 of the huntingtin gene leading to the ubiquitous expression of mutant huntingtin ( Htt ) 4. It is characterized by progressively worsening motor and nonmotor deficits including cognitive abnormalities (which over time lead to dementia), neuropsychiatric symptoms,5 weight loss,6 and sleep and circadian disturbances (for a review see Videnovic et al7). Although pathogenic pathways are beginning to be unraveled offering targets for treatment,8 the precise pathophysiological mechanisms of HD are poorly understood 9.…”

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“…Besonders ausgeprägt ist der Gewichtsverlust in der späten hypokinetischen Krankheitsphase der Huntingtonkrankheit [184]. Aber ein unbeabsichtigter Gewichtsverlust tritt auch schon in frühen Krankheitsstadien auf [185]. In einer Studie, in die 517 Patienten mit Huntingtonkrankheit im frühen Stadium eingeschlossen wurden, korrelierte das Ausmaß des Gewichtsverlustes direkt mit der CAG-Repeat-Länge, wohingegen sich keine Korrelationen des Gewichtsverlustes mit motorischen, kognitiven oder Verhaltenssymptomen fanden [186].…”