Huntington disease is a rare genetic disorder that is characterized by uncontrolled movements, emotional problems, and loss of thinking ability

1. Huntington’s Disease
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Mansi Sehgal
RA1711014010099
It is an inherited neurodegenerative disease in which
brain cells are damaged and die overtime leading to
progressive loss of mental and physical abilities.

2. History
• Huntington’s disease was first recognised by George Huntington in
1872.
• He presented his first paper called On Chorea.
• The paper was later published in Medical and Surgical Reporter of
Philadelphia and the disorder he described became known as
Huntington’s chorea
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3. Prevalence of the disease
• Studies have found that, in terms of CAG repeats, Western nations have
individuals presenting far higher numbers of repeats than Asian countries.
• The disease is still not recognised in India but as per the scientists it affects 3 to 7
people among 100,000 people.
• The highest frequencies of HD are found in Europe and countries of European
origin, such as the United States and Australia.
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4. Clinical symptoms of the disease
Early symptoms-
• Difficulty in concentration
• Clumsiness
• Mood swings
• Depression
• Stumbling
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5. Symptoms developed later –
• Involuntary jerking or fidgety movements (chorea)
• Difficulty speaking clearly
• Swallowing problems
• Slow movements (Athetosis)
• Lack of flexibility
• Lack of impulse control
• Difficulty moving around
• Lack of awareness
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6. Genetics of the disease
• Huntington’s disease is an autosomal dominant
disorder which means that a person needs only
one copy of the defective gene to develop the
disorder.
• A parent with a defective gene could pass
along the defective copy of the gene or the
healthy copy
• Each child in the family, therefore, has a 50
percent chance of inheriting the gene that
causes the genetic disorder.
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7. Genes involved
• The disease is caused by the HTT gene located on the short (p)
arm of chromosome 4 at position 16.3
• It contains a triplet repeat – CAG
• The HTT gene provides instructions for making a protein called
huntingtin. Although the exact function of this protein is unknown,
it appears to play an important role in nerve cells (neurons) in the
brain and is essential for normal development before birth.
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8. Mutations
• It is a Trinucleotide repeat disorder- a genetic disorder caused by trinucleotide
repeat expansion, a kind of mutation in which repeats of three nucleotides
(trinucleotide repeats) increase in copy numbers until they cross a threshold
above which they become unstable.
• In normal people a triplet repeat(CAG) called Huntingtin(HTT) is repeated
10-35 times in a row.
• CAG codes for glutamine.
• People with Huntington’s disease will have repeats more than 36 times
meaning they will have more glutamine in a row.
• This causes fragmentation and aggregation forming misfolded proteins –
polyglutamine.
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9. Mutations
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10. • This polyglutamine is toxic to nerve cells and aggregate in the
dorsal striatum of the brain causing neuronal cell death
• The dorsal striatum includes caudate and putamen, and overtime if
enough of the neurons die here, it can cause loss of brain tissue
volume in that area and expansion of lateral ventricles
• The function of dorsal striatum is to inhibit the unwanted
movements- its degeneration causes dance like movements known
as chorea
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11. • The expanded CAG repeats affects the DNA replication
• The repeating sequences may also form loops where the DNA polymerase can
add extra CAG repeats.
• This means that a child of a parent with HD can inherit more repeats than the
parent did.
• So if a father has 40 repeats, he will pass on 45-50 repeats to his child.
• If there are more repeats, earlier the age when a person starts having
symptoms- Genetic Anticipation.
• People with 36 to 39 CAG repeats may or may not develop the signs and
symptoms of Huntington disease.
• while people with 40 or more repeats almost always develop the disorder.
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12. Types-
Juvenile Huntington’s disease-
• Less common, early-onset form of Huntington disease that begins in
childhood or adolescence.
• Juvenile HD is defined by the onset of symptoms before age 20 years and
accounts for 5-10% of all HD cases.
• Most often, children with juvenile HD inherit the mutation repeat from their
fathers, although on occasion they inherit it from their mothers.
• Juvenile Huntington disease has a rapid disease progression once symptoms
occur.
• In some cases, behaviour problems are the first symptom in a teenager with
juvenile HD and chorea may be only mild or not present at all. The symptoms
in people with juvenile HD generally worsen more quickly than in those with
adult-onset HD, often leading to loss of life within 10 to 15 years after
symptoms begin. 12

13. Adult Huntington’s disease-
• Adult-onset Huntington disease, the most common form of this disorder, usually
appears in a person’s 30’s or 40’s.
• Early signs and symptoms can include irritability, depression, small involuntary
movements, poor coordination, and trouble learning new information or making
decisions.
• Individuals with the adult-onset form of Huntington disease usually live about 15
to 20 years after signs and symptoms begin.
• Affected individuals may have trouble walking, speaking, and swallowing. People
with this disorder also experience changes in personality and a decline in thinking
and reasoning abilities.
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14. 5 stages of HD-
• Early stage- During the early stage, the patient already has been diagnosed
with Huntington’s disease, but is fully functional at home and at work.
• Early intermediate stage- In the early intermediate stage, the patient is still
functional at work, but at a lower capacity.
• Late intermediate stage- patient no longer can conduct work or manage
household responsibilities.
• Early advanced stage- The patient is not independent at this stage, will
require substantial assistance in financial affairs, domestic responsibilities,
and most activities of daily living
• Advanced stage -patients with Huntington’s disease at the advanced stage
need total support in daily activities from professional nursing care.
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15. Diagnosis
Brain imaging and function-
• The imaging technologies may include magnetic resonance imaging
(MRI) or computerised tomography (CT) scans that provide detailed
images of brain structures.
• These images may reveal structural changes at particular sites in the
brain affected by Huntington's disease
Genetic counselling and testing-
• This test can confirm the diagnosis, and it may be valuable if there's
no known family history of Huntington's disease
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16. Treatment
There is no treatment to stop or reverse Huntington's disease,
however there are some medications that can help keep symptoms
under control.
• Tetrabenazine - to suppress the involuntary jerking and writhing
movements (chorea) associated with Huntington's disease
• Antipsychotic drugs- such as risperidone, olanzapine, or
haloperidol.
• citalopram- helps with depression
• Mood-stabilizing drugs - prevent the highs and lows associated
with bipolar disorder.
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17. • Psychotherapy- a psychotherapist can provide talk therapy to help
a person manage behavioural problems, communication problems,
etc.
• Speech therapy- HD can impair control of muscles of mouth and
throat, so a speech therapist can help.
• Physical therapy – safe exercises that enhance strength,
flexibility, balance and coordination.
• Occupational therapy- use of assistive devices is encouraged that
improve functional abilities like handrails at home, eating and
drinking utensils for people with limited fine motor skills.
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18. Famous People Affected
• Woodrow Wilson Guthrie (July 14, 1912
– October 3, 1967) was an American
singer-songwriter.
• He died at the age of 55 suffering from
Huntington’s disease.
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19. Societies working on this:
• Huntington’s Disease Society of America (New York)
• Hereditary disease foundation (New York)
• Huntington Disease society (India)
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