Huntington disease (HD) is an autosomal dominant neurodegenerative disorder with midlife onset characterized by psychiatric, cognitive, and motor symptoms. Death occurs between 12 and 15 years from the time of symptomatic onset.

The HD mutation was identified in 1993 as an unstable expansion of CAG (trinucleotide) repeats within the coding region of the gene" IT15"(for" Interesting Transcript"). This gene, on chromosome 4 (4p63), encodes the protein huntingtin (1). The mutation in huntingtin produces an expanded stretch of glutamine residues attached to its NH2-terminal. The function of normal huntingtin and the mechanism of pathogenesis caused by polyglutamine expansion in mutant huntingtin are unknown. Interestingly, the abnormal huntingtin still retains some of the basic functions of the normal huntingtin since individuals homozygous for the HD gene produce only mutant huntingtin and yet appear to have the same clinical features as heterozygous HD patients. The abnormal huntingtin is ubiquitous in somatic tissues, yet the pathology of HD is apparently restricted to the brain, where degeneration occurs initially in the striatum and cortex and eventually may appear throughout the brain. Among the theories for the selective cellular damage in HD, the most compelling involve abnormal energy metabolism and excitotoxicity.