Huntington Disease (HD) is a progressive neurodegenerative disease characterized by chorea, emotional disturbances, and cognitive problems. Most common is the adult-onset form of the disease, which presents itself in the third or fourth decade of the affected individual's life. Initially, the disease may start off as mild balance problems, clumsiness, mood swings, mild uncontrolled movements in the fingers and toes, and involuntary facial movements. However, as the disease progresses, the severity of the problems increases, and affected patients show severe gait, balance and co-ordination problems, impaired judgment, memory and cognition, severe chorea, slurred speech, and difficulty in swallowing and eating. Most patients survive up to 10 to 15 years after the symptoms appear. There is also a juvenile form of the disease, although rare, which manifests itself at as early as 3-years of age. This form is usually more severe and progresses faster than the adult-onset form. About 30-50% of patients affected by the juvenile form display seizures in addition to the general symptoms of HD.
The disease is more common among Caucasian populations, where 7-10 of every 100,000 individuals are affected. Genetic analysis of the Huntingtin gene is used to diagnose the disease. In fact, screening of this gene can also identify at-risk individuals. Management of the disease is difficult. Imaging techniques show a distinctive pattern with loss of neurons, especially in the caudate and putamen. Tranquilizers, anti-psychotic drugs, and anti-depression medications can help. However, most of these medications have a number of side effects including fatigue, restlessness, and imparting rigidity and stiffness. Speech, physical, and occupational therapy may help in later stages of the disease. Long-term care services may also be required in later stages.
HD is caused due to a specific type of mutation in the Huntingtin gene. The gene is located on the short arm of chromosome 4, where it spans a length of approximately 17 kb of DNA. The normal gene codes for a protein with 3144 amino acids, weighing approximately 347 kDa. Although the exact function of this protein is not known, it is speculated that it plays major roles in intracellular organelle or axonal transport, and in the generation and expression of hematopoietic cells.
The HD gene contains an unstable CAG repeat toward the 5' end of the coding region, which in normal cases, extends to a length of 10 to 35 repeats. In individuals affected with HD however, this repeat occurs from 36 to 120 times. The protein produced by such abnormal genes, therefore, contains a long stretch of glutamine, which interferes with the normal functioning of the protein. The effect is most severe in neuronal cells, where loss of function of this protein results in cell death, and resulting in the signs and symptoms typical of HD. Interestingly, this repeat length is commonly seen to expand in successive generations, but has also been in some cases to contract.