Early symptoms of Huntington’s are classified inthree domains: psychiatric, cognitive and motor. The motor symptoms are gradualand occur during early stages of the disease. The symptoms are mostly muscle”spasms” with involuntary movements of chorea. These involuntary movements areof ‘small degree’ (Peggy C 2016) whichgradually get worse. In early stages of the disease, motor symptoms tend toonly be hyperkinetic however as the disease progresses, motor symptoms arehyperkinetic with dystonia and bradykinesia.
In terms of cognitive dysfunction,HD causes a major decline in the ability to making decisions, organisation,plan and multitask. Both short term and long-term memory is also impaired. Asthe disease persists, cognitive deficits results in the diagnosis of dementia.
Psychiatric symptoms at early stages of HD are in the domain of frontaldisinhibition. The symptoms include, irritability which results in severeoutbursts of anger, alterations in mood, impulsivity and poor attention. Familymembers often recognise personality change. Later in the disease family membersusually interpret the symptoms as depression. Huntington’s disease is caused bya mutation in chromosome 4, that encodes for Huntingtin’s protein, of aperson’s DNA. Huntingtin gene contains CAG trinucleotide sequence which codesfor glutamine hence adds glutamines to the Huntingtin protein. In peoplewithout HD, CAG is repeated fewer that 35 times.
People with more than 36 CAGrepeats develop the disease. This then results in an increase in glutamine blocks.For example, a person has 43 CAG repeats will produce a huntingtin protein with43 glutamine blocks at the start. (UCL2011) If a huntingtin protein consists of too many glutamine blocks itresults in a different shape and behaves differently from the normal protein.The mutated protein has an impact on neuronal health and tends to foldinaccurately then accumulate as inclusion bodies. These bodies also contain proteinsthat control transcription, protein synthesis, folding and degradation. Also,the number of CAG repeats determines how the huntingtin protein interacts withits interactor proteins: HIP-1 and HAP-1.
As CAG repeats increase in number,the huntingtin protein binds more to HAP-1 and less to HIP-1. (Liou 2010) The abnormal huntingtinprotein binds tightly to HAP-1 than the normal huntingtin protein which causesharm to cells and primarily affects striatal and cortical neurons that areinvolved in controlling voluntary movement, cognition and motor planning. Whennerve cells in the striatum malfunction and die it causes over-stimulation ofthe motor cortex. As this progressively occurs, patients develop irregular involuntarymovements of chorea. It also causes other symptoms of HD for example, gradualneuronal loss throughout the frontal lobe and cortex results in cognitivedysfunction.
(Driver-Duckley, N. Caviness2007)