Huntington’s Disease: Causes, Symptoms, Diagnosis And Treatment

Wednesday, May 29, 2019, 12:20

Huntington's disease is a progressive brain disorder that is caused by a defective gene. Changes occur in the central area of the brain, in turn, affecting movement, mood and thinking abilities. The defect is considered dominant. When a child inherits it from a parent having Huntington's disease, he or she is sure to eventually develop the disease.

Huntington's disease is named after George Huntington, the physician who described this disorder first during the late 1800s. For most of the cases, the first signs begin to show between the ages of 30 and 50 years. Read on to gain more insights on this defect.

What Is Huntington's Disease?

This is an inherited disease that causes the progressive degeneration of nerve cells in the brain ^[1] . When this disease develops before the age of 20 years, the condition is called juvenile Huntington's disease ^[2] . This defect results in the drastic deterioration of a person's physical and mental abilities. This defect is caused by a single defective gene on chromosome 4 (one of the 23 human chromosomes that carry a person's entire genetic code) ^[3] .

The defective gene codes the blueprint for a protein called huntingtin ^[4] . This defective huntingtin protein causes brain changes that result in abnormal involuntary movements, depression, a severe decline in reasoning abilities, extreme irritability and other mood changes.

Causes Of Huntington's Disease

It is caused by an inherited defect in a single gene. This condition is an autosomal dominant disorder (a person would need only one copy of the defective gene to develop this defect) ^[5] . A parent having a defective gene can pass on either the defective copy of the gene or the healthy copy. Therefore, each child in the family holds a 50 per cent chance of inheriting the gene that causes this genetic disorder.

Research says that the huntingtin gene defect involves extra repeats of one specific chemical code in one small section of chromosome 4. Under normal circumstances, the huntingtin gene includes 17 to 20 repetitions of this code. In case of the defect, there are 40 or more repeats ^[6] . When genetic tests are conducted to determine this disorder, the number of repeats present in an individual's huntingtin protein gene is measured.

Symptoms Of Huntington's Disease

The prime symptoms can be related to movement, cognitive and psychiatric disorders.
Movement disorders: It can include both involuntary movement problems and impairments in voluntary movements. These usually include the following ^[7] :

Muscular problems such as dystonia
Involuntary jerking movements
Abnormal eye movements
Impaired gait, balance and posture
Difficulty during speech or swallowing

Cognitive disorders: The cognitive impairments associated with this disorder include the following ^[8] :

Difficulty in learning new information
Difficulty organizing or prioritizing tasks
Lack of flexibility
Outbursts due to lack of impulse control
Lack of awareness of one's abilities
Slowed down processing power

Psychiatric disorders: The most common disorder is depression, which occurs due to an injury of the brain or due to changes in the brain's functionality. The following are the major signs ^[9] :

Social withdrawal
Fatigue
Loss of energy
Suicidal thoughts
Insomnia
Feeling irritated and sad

Other common psychiatric disorders include mania, obsessive-compulsive disorder and bipolar disorder.
Weight loss is also common in people with Huntington's disease ^[10] . There could be severe risks of choking during the later stages of this disorder.

Symptoms of juvenile Huntington's disease: The start and progression of this disorder in younger people can be slightly different than that in adults. The following early signs can be observed ^[11] :

Changes in fine motor skills
Seizures
Contracted and rigid muscles
Tremors
Behavioural problems
Loss of previously learnt physical or academic skills
A rapid drop in school performance.

Complications Associated With Huntington's Disease

Being unable to do things that were quite easy earlier can lead to depression and frustration. Extreme weight loss can turn a person's immune system very weak ^[12] . This would make the person more vulnerable to infections. Although Huntington's disease itself is not fatal, choking, pneumonia, etc. can lead to death.

The clinical depression associated with Huntington's disease can increase the risk of suicide. As the disease progresses, the patient would need help with all activities of daily life. Later stages of the disease involve the person being confined to the bed and unable to speak.

Studies reveal that the time from this disorder's emergence to the death of the suffering person is often about 10 to 30 years ^[13] . In the case of juvenile Huntington's disease, death usually occurs within 10 years after symptoms develop ^[14] .

Diagnosis Of Huntington's Disease

A preliminary diagnosis is conducted based on the person's answers to questions followed by a general examination, review of the family history and neurological and psychiatric examinations. The following methods are used to reach a conclusive diagnosis:

1. Neurological examination: Followed by a questionnaire, your neurologist would conduct simple tests to judge the following ^[15] :

Motor symptoms: These include checking for muscle strength, reflexes, balance, coordination and muscle tone.

Sensory symptoms: These include testing for hearing, sense of touch, vision and eye movement.
Psychiatric symptoms: These include testing for mood and mental status.

2. Neuropsychological testing: The following standardized tests are performed for assessment ^[16] :

Reasoning
Mental agility
Language function
Spatial reasoning
Memory

[HD memory image]

3. Psychiatric evaluation: Your doctor may ask you to consult a psychiatrist who can judge various factors that are essential to contribute to your diagnosis. These include the following ^[17] :

Coping skills
Emotional state
Patterns of behaviour
Quality of judgement
Evidence of substance abuse
Signs of disordered thinking

4. Genetic counselling and testing: If symptoms are strong enough, your doctor may ask you to go for a genetic test for the defective gene ^[18] . This test can confirm the diagnosis. This test is quite beneficial if there is no known family history of Huntington's disease.

5. Predictive genetic test: A person who has a family history of this disease but does not show any signs of it can be given a predictive genetic test. Although this form of testing does not provide any treatment benefit. Few might want to do it just to be sure that they do not have this disorder ^[19] . However, such genetic forms of testing can only be performed after consultation with a genetic counsellor.

6. Brain imaging and function: There might be a need to assess the structure or function of the brain. This is done through brain-imaging tests. The imaging techniques used include MRI or CT scans ^[20] . The resulting images may indicate structural changes in particular regions of the brain.

Treatment For Huntington's Disease

Currently, there is no treatment for this defect ^[21] . There is no cure for reversing its progression or slowing it down. Nevertheless, symptoms can be managed with therapies and medications.

Medications: Management of the symptoms through medication evolve over the course of the disease. Medicines are known to lessen some symptoms of movement and psychiatric disorders. However, the drugs used can cause certain side effects. The usual medications prescribed are as follows:

Tetrabenazine: This suppresses the involuntary movements ^[22] . A serious side effect of this involves worsening depression.

Antipsychotic drugs: These are beneficial in treating chorea (a neurological disorder that is characterized by jerky involuntary movements) ^[23] . However, as a side effect, it can lead to worsening of involuntary contractions.

Medications to suppress chorea: Amantadine, levetiracetam and clonazepam are known to work very well in treating chorea ^[24] . However, at high doses, amantadine can worsen the cognitive effects of this disorder. Levetiracetam causes nausea, mood swings and stomach upset. Clonazepam has a high risk of dependence and abuse.

Medications for psychiatric disorder:

Antidepressants such as citalopram, fluoxetine and sertraline can be used to treat obsessive-compulsive disorder ^[25] . Side effects might include diarrhoea, drowsiness and low blood pressure. Antipsychotic drugs such as quetiapine, risperidone and olanzapine can be used to suppress violent outbursts and other various mood disorders. Mood-stabilizing drugs such as anticonvulsants can help in the prevention of the highs and lows associated with bipolar disorder.

Psychotherapy: Talk therapy is provided to the person to manage behavioural issues ^[26] . Such a therapy can also help in developing coping strategies, management of expectations during the progression of the disease and facilitate effective communication among family members.

Speech therapy: A therapist can work towards the improvement of the patient's ability to speak clearly ^[27] . Speech therapists can also work with resolving issues related to eating and swallowing.

Physical therapy: Appropriate and safe exercises can enhance the patient's strength, balance, flexibility and coordination ^[28] . The use of supports to improve posture can help lessen the severity of some movement problems.

Occupational therapy ^[28] : Family members of the patient can be taught the benefits of using assistive devices to improve the functional abilities of the person with the defect. Use of handrails at home, using eating utensils adapted for people with limited fine motor skills and the use of devices for providing assistance during a bath, etc. can go a long way in preventing limitations when it comes to daily life routines of the person with the disorder.

Huntington's Disease Managing Tips For The Caregiver

The following tips might be helpful for the person who is responsible for taking care of someone who is suffering from Huntington's disease:

Provide more than three meals a day as the person with this defect would have higher caloric needs due to physical exertion or unknown metabolic problems ^[29] .
Provide foods that are easier to eat. Use utensils designed for people with limited fine motor skills.
Maintain a calendar to keep a regular routine.
Break down tasks for the patient into manageable steps.
Create a calm and simple environment.
Identify and avoid stressors that can trigger outbursts ^[30] .

On A Final Note...

Managing Huntington's disease is demanding not just for the person suffering with it but also for his or her family members. As the disease progresses, the person would only become more dependent on the caregiver. Talking to the doctor openly will help you understand strategies that can help while coping with this ailment.

Scientists hope to find a solution to this disease in the form of gene therapy. Research is extensively underway to find a possible way out to cure, prevent or at least slow down Huntington's disease.

View Article References

[1] Nopoulos P. C. (2016). Huntington disease: a single-gene degenerative disorder of the striatum.Dialogues in clinical neuroscience,18(1), 91–98.
[2] Quigley, J. (2017). Juvenile Huntington’s disease: diagnostic and treatment considerations for the psychiatrist.Current psychiatry reports,19(2), 9.
[3] Bouchard, C. (1994).The genetics of obesity. CRC press.
[4] Schulte, J., & Littleton, J. T. (2011). The biological function of the Huntingtin protein and its relevance to Huntington's Disease pathology.Current trends in neurology,5, 65–78.
[5] Bernhardt, B. A., Zayac, C., & Pyeritz, R. E. (2011). Why is genetic screening for autosomal dominant disorders underused in families? The case of hereditary hemorrhagic telangiectasia.Genetics in medicine : official journal of the American College of Medical Genetics,13(9), 812–820.
[6] Roos, R. A. (2010). Huntington's disease: a clinical review.Orphanet journal of rare diseases,5(1), 40.
[7] Squitieri, F., Berardelli, A., Nargi, E., Castellotti, B., Mariotti, C., Cannella, M., ... & Ruggieri, S. (2000). Atypical movement disorders in the early stages of Huntington's disease: clinical and genetic analysis.Clinical genetics,58(1), 50-56.
[8] Paulsen J. S. (2011). Cognitive impairment in Huntington disease: diagnosis and treatment.Current neurology and neuroscience reports,11(5), 474–483.
[9] Julien, C. L., Thompson, J. C., Wild, S., Yardumian, P., Snowden, J. S., Turner, G., & Craufurd, D. (2007). Psychiatric disorders in preclinical Huntington's disease.Journal of neurology, neurosurgery, and psychiatry,78(9), 939–943.
[10] Aziz, N. A., Van Der Burg, J. M. M., Landwehrmeyer, G. B., Brundin, P., Stijnen, T., Roos, R. A. C., & EHDI Study Group. (2008). Weight loss in Huntington disease increases with higher CAG repeat number.Neurology,71(19), 1506-1513.
[11] Quarrell, O. W., Nance, M. A., Nopoulos, P., Paulsen, J. S., Smith, J. A., & Squitieri, F. (2013). Managing juvenile Huntington's disease.Neurodegenerative disease management,3(3), 10.2217/nmt.13.18.
[12] Olejniczak, M., Urbanek, M. O., & Krzyzosiak, W. J. (2015). The role of the immune system in triplet repeat expansion diseases.Mediators of inflammation,2015, 873860.
[13] Tang, C., & Feigin, A. (2012). Monitoring Huntington's disease progression through preclinical and early stages.Neurodegenerative disease management,2(4), 421–435.
[14] Sunwoo, J. S., Lee, S. T., & Kim, M. (2010). A case of juvenile huntington disease in a 6-year-old boy.Journal of movement disorders,3(2), 45–47.
[15] McCusker, E., Richards, F., Sillence, D., Wilson, M., & Trent, R. J. (2000). Huntington’s disease: neurological assessment of potential gene carriers presenting for predictive DNA testing.Journal of clinical neuroscience,7(1), 38-41.
[16] Panegyres, P. K., & Goh, J. G. (2011). The neurology and natural history of patients with indeterminate CAG repeat length mutations of the Huntington disease gene.Journal of the neurological sciences,301(1-2), 14-20.
[17] Clabough E. B. (2013). Huntington's disease: the past, present, and future search for disease modifiers.The Yale journal of biology and medicine,86(2), 217–233.
[18] Nance, M. A. (2017). Genetic counseling and testing for Huntington's disease: A historical review.American Journal of Medical Genetics Part B: Neuropsychiatric Genetics,174(1), 75-92.
[19] Muthane U. (2011). Predictive genetic testing in Huntington's disease.Annals of Indian Academy of Neurology,14(Suppl 1), S29–S30.
[20] Niccolini, F., & Politis, M. (2014). Neuroimaging in Huntington's disease.World journal of radiology,6(6), 301–312.
[21] Wild E. J. (). Huntington's Disease: The Most Curable Incurable Brain Disorder?.EBioMedicine,8, 3–4.
[22] Paleacu D. (2007). Tetrabenazine in the treatment of Huntington's disease.Neuropsychiatric disease and treatment,3(5), 545–551.
[23] Burke, R. E., Fahn, S., Mayeux, R., Weinberg, H., Louis, K., & Willner, J. H. (1981). Neuroleptic malignant syndrome caused by dopamine‐depleting drugs in a patient with Huntington disease.Neurology,31(8), 1022-1022.
[24] Coppen, E. M., & Roos, R. A. (2017). Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease.Drugs,77(1), 29–46.
[25] Then, C. K., Liu, K. H., Liao, M. H., Chung, K. H., Wang, J. Y., & Shen, S. C. (2017). Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes.Oncotarget,8(70), 115490–115502.
[26] La Spada A. R. (2018). A Novel Therapy for Huntington's Disease.Cerebrum : the Dana forum on brain science,2018, cer-11-18.
[27] Skodda, S., Schlegel, U., Hoffmann, R., & Saft, C. (2014). Impaired motor speech performance in Huntington’s disease.Journal of Neural Transmission,121(4), 399-407.
[28] Bilney, B., Morris, M. E., & Perry, A. (2003). Effectiveness of physiotherapy, occupational therapy, and speech pathology for people with Huntington's disease: a systematic review.Neurorehabilitation and neural repair,17(1), 12-24.
[29] Marder, K., Zhao, H., Eberly, S., Tanner, C. M., Oakes, D., Shoulson, I., & Huntington Study Group (2009). Dietary intake in adults at risk for Huntington disease: analysis of PHAROS research participants.Neurology,73(5), 385–392.
[30] Pla, P., Orvoen, S., Saudou, F., David, D. J., & Humbert, S. (2014). Mood disorders in Huntington's disease: from behavior to cellular and molecular mechanisms.Frontiers in behavioral neuroscience,8, 135.