INTRODUCTION

     HD is a progressive neurological disorders usually leading to death 15-20 years after onset of neurological or psychological impairment. In 1/2 to 3/4 of patients the initial symptoms are neurological in nature. In the remainder of cases early mental status changes may herald onset of HD, manifesting as increased irritability, moodiness, and antisocial behavior.
    This disease usually leads to death 15-20 years after onset of neurological or psychological impairment. In 1/2 to 3/4 of patients the initial symptoms are neurological in nature. In the remainder of cases early mental status changes may herald onset of HD, manifesting as increased irritability, moodiness, and antisocial behavior.
    The age of onset for symptoms is generally 30-50 years.  However, in up to 10% of patients, onset may occur before age 20 and is known as juvenile Huntington's Disease or Westphal variant.
    The prevalence in the US is 5.15 per 100,000. Clusters do exist in U.S. and overseas. The prevalence is similar in countries derived from European settlement. The disease is found in all ethnic groups.
 

MOLECULAR BIOLOGY OF THE DISEASE

    The gene which when disordered causes Huntington's disease was finally isolated in 1993. However, the mechanism by which the genetic change in the gene results in the characteristic neurodegeneration is presently unknown.
    The genetic basis of the disease is an amplification in gene with an unknown function. A triplet (CAG) is repeated 20-50 times in asymptomatic individuals; having more than 50 repeats is associated with disease symptoms. This amplification can be detected by a restriction enzyme digestion and Southern blot analysis, since the size of the fragment bound by the probe is increased as a result of the amplification of the triplet repeat.
    The mode of inheritance of the disorder is "autosomal dominant" which means that the defective gene is located on one of the paired chromosomes (chromosome 4 in this case). This results in no sex-bias in inheritance. A person with the disease (or who carries the defective gene but does not yet have symptoms) will pass on the disorder, on average, to half of his or her children.
 

Image 1: CT of patient with advanced Huntington's Disease. Notable is diffuse cortical atrophy selective atrophy of the caudate nuclei as shown by the excessive width and flattening of the lateral portion of the lateral ventricles.
 

Image 2: Sagital image of the brain of another patient diagnosed with Huntington's disease.

SYMPTOMS AND TREATMENT

    Adult onset HD can be roughly divided into three stages. Early in the disease, manifestations include subtle changes in coordination, perhaps some minor involuntary movements, difficulty thinking through problems, and, often, a depressed or irritable mood. In the middle stage, chorea may become prominent, and difficulty with voluntary motor activities will be more evident with worsening dysarthria and dysphagia. As cognitive deficits increase, the patient will be unable to hold a job or carry out most household responsibilities. Patients with late-stage disease may have severe chorea, but are more often rigid and bradykinetic. They are largely nonverbal and bedridden, with a more global dementia, although retaining a significant degree of comprehension. Psychiatric disorders may appear at any time during the course of the disease, even years before motor symptoms develop.

    The most common disturbances in emotion are depressive disorders, irritability, and apathy. Schizophrenia-like symptoms occur less frequently. These disorders have a variety of behavioral manifestations including aggressive outbursts, impulsiveness, social withdrawal, and suicidal behavior.
    Disturbances of cognition or intellect are characterized initially by a loss of cognitive speed and flexibility. This is often seen in the workplace where the patient is unable to keep up with work and becomes frustrated when required to alternate between different tasks. Cognitive losses accumulate progressively. In very advanced disease, most areas will be affected with only a few cognitive functions spared, and these become very difficult to assess.
    The motor disorder is characterized by both voluntary and involuntary movements, especially chorea. Although chorea is the most characteristic movement disorder of HD, the disturbance in voluntary movements is, in fact, more related to functional disability. Patients develop diminished manual dexterity, slurred speech and swallowing difficulties, and ultimately become rigid and unable to initiate any movements voluntarily. Patients who survive to this advanced state become confined to bed and are unable to participate in their self care.

    There is no known medical cure, however there are treatments available. Chorea may be suppressed with drugs, but is seldom worth the associated side effects. Most patients are untroubled by the choreic movements. Suppression of the movements does not result in improved function. Haloperidol (0.5-10 mg/day) may suppress chorea but will be accompanied by sedation, anticholinergic side effects, or rigidity.
    Depression is common and may require treatment. Serotonin re-uptake inhibitors or cyclic antidepressants may be tried. Irritability and explosive behavior are problems in some patients. Carbamazepine or valproate may be useful. The emergency physician should speak with the patient’s physician before initiating such treatment.
    Although there is drug therapy available, treatment must focus on specific emotional, cognitive, and motor symptoms. Symptoms will vary among patients, and will vary depending upon the stage of the disease. With drug dosages, start low, go slow. Drugs effective at one stage of the disease may not be effective at another. Reevaluate a patient's medication regimen at routine intervals. Avoid using drugs as a "quick fix" or a substitute for talking to the patient or engaging in a detailed analysis of the behavior. Don't jump to use drugs they can make things worse as well as better!

LAB PROCEDURE AND GEL/BLOT INTERPRETATION

    We used the CaseIt! computer simulation to digest the DNA samples from subjects that were diagnosed with the disease with EcoRI, and then performed a Southern blot with the Huntington's probe. By comparing the sizes of the fragments of other family members bound by the probe, we determined the Huntington's gene status of Susan and her brother.
 
 

Figure 1. PCR amplified DNA from 3 patients afflicted with Huntington's Chorea  (1, 2, 3) and two patients not affected by it (4, 5).

STATEMENT TO FAMILY

    Absent a cure, being told that one is a carrier of the Huntington's Disease gene has the same serious and long term personal, familial, legal, and financial implications that have always existed. We advise the family members to refer  for genetic counseling, preferably at a genetic testing center with extensive experience in HD. We also advise the family to be aware of these special issues: behavioral changes, home safety, communication strategies, and disability issues. It is recommended that patients as well as their the family members seek group therapy.
    Although there is currently no overall remedy for this disease, professionals are in agreement that  symptom-specific, interdisciplinary approach is the best way to care, maintain and improve the quality of life for the affected individual or family.
 
 

REFERENCES

• http://www.emedicine.com/emerg/topic254.htm
• http://www.kumc.edu/hospital/huntingtons/
• http://table.jps.net/cgi-bin/cgiwrap/wuf/fetch?/pg/ov1
• http://prospero.fmc.flinders.edu.au/hd_conf/hd.html
• http://www-nmcp.med.navy.mil/neurolog/dzhuntin.htm
• http://www.ohsu.edu/cliniweb/C10/C10.228.140.79.255.html
• http://www.med.harvard.edu/AANLIB/cases/java/case11/case.html
• http://www.caregiver.org/factsheets/huntingtons.html

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