hannan huntington's disease

8/7/2019 Hannan Huntington's Disease

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Approximately 30,000 people in the United States haveHuntington's Disease, which affects men and women equally across

all ethnic and racial lines.http://www.helpguide.org/elder/huntingtons_disease.htm#treatments

http://hdroster.iu.edu/AboutHD/Images/piHDvC.jpg

Pre pared by :Prof Dr. MOHD AFIQ HANNAN (Dr. Hannan)Forensic Pathologist-to bep/s:pray for me, insya-allah, amin!


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Progressive neurodegenerativedisorder

Inherited brain disorder progressivedeterioration physical, cognitive andemotional self

CONFIRM!! ENDED WITH DEATH IN10-40 YEARS AFTER ONSET


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Mood Swings, hormonal imbalance

Impaired Cognitive Functions

Chorea


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Huntingtons Disease is caused by a gene mutation that

creates excess copies of the CAG codon which genetically

program the degeneration of the neurons of the brain.

The cells of the basal ganglia, caudate nucleus, cortex,

globus pallidus nuclei of the brain are specifically targeted in

HD.

The number of CAG codons varies and so does the severityof the disease


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http://www.scielo.br/img/fbpe/anp/v58n1/1251f3.gif

Age of onset variesbased on the number ofrepeats.

The earliest onset of

Huntingtons everdocumented was a twoyear old boy who wasfound to have nearly100 CAG repeats.

The symptoms of HDcan also develop at 55or later, in which caseit is harder torecognize.


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10% of Huntingtonscases.Usually 80-100 CAG

repeatsstiffness or rigidity injoints as opposed to chorea

for adult-onset HD1/3 of Juvenile HD

patients have recurringseizures.Believed to inherit largenumbers of repeats fromfather.


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HD occurs in about 1 out of every 10,000 Caucasian individuals

Approximately 2.5 times more individuals are at risk for the disorder because of the midlife

peak in age at onset

About 40% of those at risk actually have the gene and are too young to exhibit symptoms

HD affects males and females equally

However the juvenile form of the disease tends to be inherited from fathers


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Symptoms are frequently recognized by people who

have history with the disease, but for others

there is testing.Huntingtons can be diagnosed by a simple blood

test at any age.There are three types of tests that can be taken

to determine an HD diagnosis:Prenatal testing

Pre-symptomatic testing

Confirmatory testing


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Presymptomatic Testing: Testing for people

who are genetically at risk for getting HD.

Confirmatory Testing: Testing thatdetermines whether people who are showing

symptoms actually have HD.

Prenatal Testing: Testing used todetermine whether a fetus is at risk for

HD.http://video.on.nytimes.com/?fr_story=d962010d883be3d1278974769d1
http://video.on.nytimes.com/?fr_story=d962010d883be3d1278974769d1226cf0ed34933http://video.on.nytimes.com/?fr_story=d962010d883be3d1278974769d1226cf0ed34933http://video.on.nytimes.com/?fr_story=d962010d883be3d1278974769d1226cf0ed34933


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Amniocentesis involves testing asample of amniotic fluid from thewomb. Usually done when woman isbetween 16 and 20 weeks.

Chronic Villi Sampling: performedearlier than amniocentesis - betweenthe 10th and 12th weeks of pregnancy.In CVS, a catheter or thin needle is

inserted into the womb to extractsome of the chorionic villi - cells fromthe tissue that will become theplacenta. The chorionic villi contain thesame chromosomes as the fetus.


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Usually includes sessions devoted to:genetic counseling, a neurological exam, apsychological interview, discussion of theresults, and follow-up.

Neurological exam is meant to determinewhether the patient has any symptoms, inwhich case they may choose todiscontinue testing procedure.

Sessions are meant to ensure that theperson about to undergo testingunderstands the implications of theknowledge of the results


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It is usually strongly advised to bring a

supportive friend to all testing sessions.

It is not recommended to bring asibling of someone else who is at risk

for HD.


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The testing process is a fairly simple

blood test. The blood the presence or

absence of the HD mutation.It is encouraged that patients have

either a blood sample from a family

member who has HD or the results ofhis/her genetic test for the purpose of

confirming the diagnosis.


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Accuracy of a positive or negative test resultis almost 100% provided that another family

member is known to have the gene for HD.

Positive test results cannot predict when thesymptoms will begin.

Test results should always be confidential.


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HD generally runs its full

terminal course in 10-30

years but it has been

discovered that the earlier the

onset of HD

symptoms, the faster the

progression of the disease

Juvenile HD usually runs itscourse much faster and death

generally occurs about 10 years

after symptoms first appear.


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There is no cure for Huntingtons Disease and no treatmentto stop or reverse the course of the disease; however

there are ways to treat the symptoms that can even delay

the onset of the disease.

Medications

Proper Diet and Nutrition

Exercise


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CoQ10BDNF and RESTGlutamic acid (Glutamate)


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Huntingtons Disease is a Tri-nucleotide Repeat Disorder CAG Repeats on specific gene

It is an Autosomal Dominant disease

Not sex-linkedHD onset is found generally in adults around the

age of 40 HD is caused by a faulty gene on the 4th chromosome which

is responsible for producing the protein Huntingtin


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CAG Repeats are found on the HD gene on Chromosome >40 repeats you develop HD, children 50% chance of developing disease 36-39 repeats Grey Zone May develop HD, children may or may not

develop HD

26-35 repeats the individual will not develop HD, children may


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The HD Gene was specifically located in 1993 by

researchers at MIT, on the 4th ChromosomeIt is responsible for producing the protein

HuntingtinResearchers are not completely sure what

Huntingtin does, however they do know that it is

somehow very important for the normal functioningof Brain Cells


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The symptoms are caused by a loss of neurons in the brain that occursabout the time that disease becomes first manifest

The basal ganglia and cortex are ravaged, which can be followed up witha MRI

In the caudate nucleus, populations of enkephalin and substance P

containing medium-sized spiny GABAergic projection neurons are the firstto be affected The exhibit wilted and recurved dendritic endings and changes in the density, shape and size of the

spines.

The large acetylcholine rich or smaller somatostatin and neuropeptide Ycontaining a spiny interneurons are spared by the disease process

It is this characteristic pattern of neuronal cell loss in the basal gangliathat forms the basis for the neurophathological grading of HD


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The repeating CAG codons work to encode 8 to 36 glutamine

residues

A broken array of around 40 glutamine residues are produced

by an adjacent stretch of CAG and CCG codons

Further 3 in Exon 58, the 2642 polymorphism is responsible

for producing part of the major haplotype (closely related linkof inherited alleles).


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grams101.67amu124

=

amu1Dalton1 =

Daltons1,000kD1 = Daltons350,000kD350 =

amu350,000=


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Huntingtins exact function is not known but it is known that: It serves a vital in cellular function, acting as a housekeeper

Not required for immediate survival and function of the cell

Is required for the survival and function of the organism as a whole

The transcripts from normal and the disease allele are both

expressed in the cells and tissues of Heterozygous HD

patients.


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This suggests that the pattern of neuronal cell death in the

striatum is due to the relatively high levels of Huntingtin

expression found in medium sized neurons

But this doesnt explain why neuronal cell types in other regions of thebrain that also express high levels of huntingtin are not affected by the

disease

In neurons, huntingtin immunoreactivity is found in cytoplasm

throughout the body, axons, dentrites, and perikarya. Suggesting a role in trafficking or neurotransmission from Huntingtin


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Genetics Testing Basic Facts

100 100 100

200 200 200

300 300 300

400 400 400

Jeopardy!


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What chromosomeis the HD genelocated on?

Chromosome 4.


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What protein doesthe functional HDgene produce?

Huntingtin.


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How many CAGrepeats guaranteeHD symptoms?

40 repeats.


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What is thespecific location ofthe HD gene?

4p16.3


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True or False:patientsundergoing

presymptomatictesting are notadvised to bring aclose friend or

family member tosessions.

False; patients areadvised to bring afriend or family

member to allsessions unlessthat person is alsoat risk for HD.


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Provided that apatient has afamily member

know to have HD,how accurate isthe test for thatpatient?

Almost 100%accurate.


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What are the threetypes of testing forHD?

Presymptomatic,Confirmatory, andPrenatal


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Give three reasonsa person at risk forHD may choose

not to undergopresymptomatictesting.

Discrimination inthe workplace,personal

relationships maychange, emotionaltrauma, expenses,health insurance,

etc.


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What is Chorea? Uncontrollable,dance-likemovements of the

hands and feet.


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When do thesymptoms of HDappear?

It depends greatlyon the number ofrepeats occurring

in the patientsgenes.


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What percentageof HD cases arejuvenile HD?

About 10%.


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What are the threemain elements oftreatment for

Huntingtons?

Proper diet andnutrition, exercise,and medication.

hannan huntington's disease

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