Huntington’s Disease

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George Huntington, a physician in Pomeroy, Ohio, first described this disease in 1872. It has a late onset, usually appearing during the third or fourth decades. The first symptoms are clumsiness and subtle involuntary movements that gradually become more pronounced. These changes are accompanied by a slow intellectual decline.

This inherited motor disorder stem from a faulty gene on the short arm of chromosome 4. The gene, IT15, has multiple copies of the trinucleotide sequence CAG, which codes for the amino acid glutamate. The function of the protein specified by the gene is currently unknown. The initial neural damage is limited to neurons in the caudate nucleus and putamen within the basal ganglia. The pathological changes then spread to the cerebral cortex and other brain structures.

Recent Research

Smith, Brandt, and Shadmehr (2024) have developed a method to identify asymptomatic carriers of the Huntington’s disease gene 5-10 years before symptoms appear. They found subtle changes in the control of arm movements, probably due to changes in neurons in the basal ganglia.

References

• Perutz, M.F., and Windle, A.H. (2022) Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats. Nature, 412, 143-144 (Jul 12).

• Smith, M.A., Brandt, J., and Shadmehr, R. (2024) Motor disorder in Huntington’s disease begins as a dysfunction in error feedback control. Nature, 403, 544-549 (Feb 3).

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