Huntington's disease

1. Huntington’s Disease
Akshay Ajith Kumar
Group - 9

2. CASE STUDY
• John, a 45-year-old man, presented initially with declining memory and
concentration. As his intellectual function deteriorated during the ensuing
year, he developed involuntary movements of his fingers and toes as well as
facial grimacing and pouting. He was aware of his condition and became
depressed. He had been previously healthy and did not have a history of
any similarly affected relatives. His parents had died in their 40s in an
automobile accident.

3. John had one daughter. After an extensive
evaluation, the neurologist diagnosed his
condition as Huntington disease. The
diagnosis of Huntington disease was
confirmed by a DNA analysis showing 43
CAG repeats in one of his HD alleles
(normal, <26). Subsequent pre
symptomatic testing of his daughter
showed that she had also inherited the
mutant HD allele .
affected father and daughter both have an allele
with a full mutation (43 CAG repeats) and a
normal allele (19 and 16 repeats, respectively)

4. PEDIGREE
The daughter’s
unaffected mother
and her unaffected
paternal uncle have
HD alleles with a
normal number of
CAG repeats.

6. DEGENERATION OF BASAL GANGLIA

8. INFERENCE
Huntington's disease (HD), also known as Huntington's chorea, is an
inherited disorder that results in death (degeneration) of brain cells
Huntington's disease has a broad impact on a person's functional abilities
and usually results in movement, thinking (cognitive) and psychiatric
disorders.

9. CLINICAL FEATURES
• Progressive neurodegenerative disorder characterized by atrophy of basal
ganglia causing triad of cognitive, motor and psychiatric impairments. There
is no cure for HD.
• Inherited autosomal dominant disorder with 50% chance of inheriting
mutant gene from affected parent.
• In western European and USA prevalence higher at about 7-10 per 100,
000 affected with >150,000 at risk. Lower in Asian and African populations.

11. • Typically adult onset disorder with mean age onset 35-44 years (range 2 to 80
years).
• <20% first display symptoms of the disease after age 50 and
have a slower progression.
• <10% cases are juvenile HD with onset before age 20 years.
• Median survival after onset is 15-18 years (range 5-25 years)
with average age at death 54 years.

13. MANIFESTATIONS
• Depression
• Apathy
• Irritability/Outbursts
• Anxiety
• Impulsivity
• Obsessive-compulsive disorder
(26-52%)
• Aggressive Behavior
• Psychosis (3-12%)
• Suicide (5.7 to 13% higher than
general population)

14. HISTORY
1872 George Huntington, MD, described a
neurological disorder that later came to
bear his name
“….The hereditary chorea, as I shall call it, is
confined to certain and fortunately few
families and has been transmitted to them,
an heirloom from generations away back in
the dim past….”
“….There are three marked peculiarities of
this disease:
1.hereditary nature
2.tendency to insanity and suicide
3.manifesting itself as a grave disease in
adult life.”

15. GENOTYPE – PHENOTYPE CORRELATIONS
• There is a negative correlation between number of CAG repeats and
age of onset.
• Individuals with adult onset HD usually have 35-55 CAG repeats.
• Patients with very late onset tend to have repeats in 36-38 low
abnormal range.
• Anticipation, a phenomenon in which increasing disease severity and
earlier onset is observed in successive generations, can occur in HD
and most often through paternal transmission (instability of CAG repeat
during spermatogenesis).
• Individuals with CAG repeats 60+ often present with Juvenile HD.

17. DIAGNOSIS
Take the family history or genealogy
Using a blood sample
Undergo a brain imaging test.
Computed tomography (CT) and magnetic
resonance imaging (MRI)

18. TREATMENT
As of now there is no way to stop or reverse the course of the
disease once you are diagnosed.
Although it is possible to treat some of the symptoms.

19. Tetrabenazine- to treat the chorea
Haloperidol- antipsychotic drug
Clonazepam- alleviate choreic movements, control hallucinations and delusions.
fluoxetine sertraline, nortriptyline – for depression
Tranquilizers- help control anxiety
Lithium- for pathological excitements and severe mood swings

20. POSSIBLE NEW METHOD FOR TREATMENT
Huntington’s disease (HD) is a genetically heritable disease that destroys
‘medium spiny neurons’ (MSNs) in the brain, leading to emotional changes,
mental decline and impaired movement.
The Huntington gene makes a protein important for neurons, but scientists are still trying to
understand what this protein does in cells and why too many ‘CAG’ repeats causes MSNs to die.
Researchers are using MSNs made with induced pluripotent stem cells (iPSCs) to model HD and
observe how HD progresses. iPSCs are also used to rapidly test new HD drugs, gene therapies and
other treatments faster than before iPSCs were available.
Studies are examining how brain (neural) stem cells could be transplanted in patients’ brains to repair
the brain and possibly regrow MSNs and other needed brain cells.

21. ETHICAL CONCERN
• Ethical and reliable sources of neural stem cells must be developed. iPSCs
and embryonic stem cells may be able to make large numbers of neural
stem cells, but these cells must be uniform, predictable and safe.
• If they are not properly tested pluripotent stem cells could cause cancer or
other life-threatening complications.

22. Thank You