Huntington

Disease
a rare neurodegenerative disease

Done by: Rita Maria ALDahr

 OVERVIEW
• Huntington's Disease (HD) is an inherited neurological condition caused by a faulty gene
on chromosome 4 (IT-15) causing problems with a person’s ability to think, behave and
move.
• HD is an autosomal dominant
Over time, the disease causes progressive functional
disorder which is passed from
decline, leading to a loss of independence and the ability to
parent to a child without regard for perform daily activities.

sex and children of a person with a

defective HD gene have a 50:50
chance of inheriting the gene from
their affected parent.

• If a person does not inherit the altered gene for HD then his or her children are not at risk of
developing.
Pathophysiology
• Huntington disease results
from a mutation in
the huntingtin (HTT) gene (on
chromosome 4), causing
abnormal repetition of the
DNA sequence CAG, which
codes for the amino acid
glutamine.

• As CAG repeat series exceeds

the normal range it triggers the
formation of toxic mutant
huntingtin protein (mHTT) and
the breakdown of nerve cells in
the brain.
The risk of HD development depends on the number of CAG repeats in
the following fashion:

The same direct proportionality also

less than 36 repeats—minimal
risk
36–39 repeats—moderate risk
over 40 repeats—high risk
applies to the age of onset (typically 20–65
years) and severity of the disease, which
means that a longer CAG repeat sequence
is associated with an earlier onset of HD
and more severe symptoms
• Cellular pathologies associated with HD result in the death of striatal GABAergic neurons in the basal ganglia,
the executive center for organizing motor memory, learning and function in the brain. Specifically, progressive
and marked degeneration of caudate and putamen(stratium).

• There are different types of neurons and neurotransmitters in stratium and balanced interaction between
dopamine, acetylcholine, and GABA play vital role in regulating motor movements.
• Stratium gamma aminobutyric acid (GABA-ergic)neurons are most vulnerable to cell death in HD.
• Selective loss of these specialized cells results in decreased inhibition of the thalamus.
• Thalamus increases output to certain regions of the cerebral cortex leading to disorganized excessive
movement patterns of chorea.
• As disease progresses damage to other pathways and dopamine receptors caused decreased stimulation to
cortex and thus rigid bradykinetic features.
Diagnosis
Genetic test
During such testing, blood samples are taken from patients and
DNA is directly analysed for HD mutations. The DNA is studied
through a series of tests known as Polymerase chain reactions or
PCR testing.
During this testing, the number of CAG repeats within the IT15
gene region is estimated.
Brain imaging test (MRI, CT, PET)
SYMPTOMS
Cognitive
Language difficulties-decreased attention-
difficulty retrieving information-deficits in learning
and memory-emotional recognition problems- lack
of awareness-reduced mental flexibility-cognitive
slowing-problems with planning.

Motor
Chorea-bradykinesia-impaired
speech-impaired walking-dystonia-
akinesia-rigidity-dysphagia-poor
balance-risk falls

Behavioural
Apathy-depression-impaired judgement-
irritability-sleep problems-impulsivity-suicidality-
aggression-psychosis
Once symptoms begin, there is progressive cognitive, motor and psychiatric
impairment; with death occurring an average of 18 years after onset of symptoms.

Death for most people with Huntington's disease is usually a result of infection,
pneumonia, heart failure or choking.

The most common cause of death is pneumonia due to the individual not being
able to clear their lungs properly and having problems with swallowing, which
results in food and liquid entering their lungs.

The second most common cause of death is heart failure.

The suicide rate among HD patients is 5-10 times higher than in the general
population.
Eventually the person is unable to care for themselves and requires total nursing
care.
 TREATMENTS:
Two Eurepoean scientists made the breakthrough discovery that dopamine pathways between neurons are
destroyed in Parkinson’s disease patients. Since the symptoms of Parkinson’s disease are nearly the opposite of
those with HD, the scientists hypothesis that decreasing HD patient’s dopamine levels may be a key step in
treating the disease.
(Tetrabenazine (Xenazine) was developed specifically to reduce the severity of the jerky/involuntary
movements occurring in Huntington's disease.

Tetrabenazine acting mechanism:

Other drugs are also used to help
reduce involuntary movements –
these include neuroleptics and
benzodiazepines.

There is no effective treatment

for HD, although some
symptomatic relief may be
obtained.
While there are currently no approved medicines that can slow or stop the progression of
HD, current disease management strategies can provide symptom relief and maximize
function.

Psychotherapy Speech Therapy Physical therapy Occupational therapy

References
Huntington's Disease Society of America. Overview of HD. https://hdsa.org/what-is-hd/overview-of-
huntingtons-disease/. Last accessed May 2, 2019.

Frank S. Treatment of Huntington's disease. Neurotherapeutics. 2014;11(1):153-160.

Huntington's Disease Society of America. Understanding behavior in Huntington's disease: a guide for
professionals http://hdsa.org/wp-content/uploads/2015/03/Understanding-Behavior.pdf . Last accessed
May 2, 2019.

National Institute of Health (NIH). Huntington disease. https://ghr.nlm.nih.gov/condition/huntington-

disease#inheritance. Last accessed May 2, 2019.