Approximately 30,000 people in the United States have Huntington's Disease, which affects men and women equally across all ethnic and racial lines. http://www.helpguide.org/elder/huntingtons_disease.htm#treatments

Cable/DSL (3.38MB)http://hdroster.iu.edu/AboutHD/Images/piHDvC.jpg

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Mood Swings

Impaired Cognitive Functions

Chorea

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 and cortex of the brain are specifically targeted in HD.

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

http://www.scielo.br/img/fbpe/anp/v58n1/1251f3.gifAge of onset varies based on the number of repeats.

The earliest onset of Huntingtons ever documented was a two year old boy who was found to have nearly 100 CAG repeats.

The symptoms of HD can also develop at 55 or later, in which case it is harder to recognize.

10% of Huntingtons cases.Usually 80-100 CAG repeatsstiffness or rigidity in joints as opposed to chorea for adult-onset HD 1/3 of Juvenile HD patients have recurring seizures.Believed to inherit large numbers of repeats from father.

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 testingPre-symptomatic testingConfirmatory testing

HD generally runs its full terminal course in 10-30 years but it has been discoveredthat the earlier the onset of HD symptoms, the faster the progression of the diseaseJuvenile HD usually runs its course much faster and death generally occurs about10 years after symptoms first appear.

There is no cure for Huntingtons Disease and no treatment to 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.MedicationsProper Diet and NutritionExercise

CoQ10BDNF and REST

My husband knew he had a 50% chance of inheriting the disease from the age of seven. We married at age 35 and he kept the ravages of the disease to himself. I noticed then, 21 years ago that his foot moved most of the time. I also noticed he did not swing his arms when walking, hiking, ect. While working on my Masters Degree in Counseling, my research led me to information on neurological disease and a chill went up my spine when I read of tics and inability to move arms when walking. I tried to talk to him about it, but he turned his back to me and didnt talk. Finally, from a niece who developed HD young and rapid progression, I was able to learn from a previously estranged sister in law the whole family history. I knew in my mind and heart my husband had inherited the disease. He was becoming depressed and lost three jobs in succession. Now, it is 21 years later since I noticed his foot moving. He is bedridden, incontinent, has pureed food, etc. He cannot walk and his speech is slurred past recognition. The saddest part is that he stays angry and will lash out with no warning. I have been hit many, many times just trying to help him eat or change his depends. I have an aide in the morning hours. He gets along with her. However, this service is expensive and deleting our savings. I have had back surgery from lifting him and now I need a total knee replacement but cant leave him with anyone for three days hospitalization. This disease affects the family and the caregiver, which is myself. I know it is a horrible life my husband is living and I do not complain. I have tried four different nursing homes but his violent behavior has caused him dismissal. I love him dearly and really do not want him placed in a State Hospital where he will not have all the attention, good food, careful inspection for bedsores and medicine pulverized in his favorite puddings. At this point, I am at my wits end. I am bi-polar and fight depression and mania myself. I have laid down my life for a friend but when will it ever end.

http://livingwith.neurologychannel.com/huntingtons-disease/20070919_2571

Huntingtons Disease is a Tri-nucleotide Repeat DisorderCAG Repeats on specific geneIt is an Autosomal Dominant diseaseNot sex-linkedHD onset is found generally in adults around the age of 40HD is caused by a faulty gene on the 4th chromosome which is responsible for producing the protein Huntingtin

CAG Repeats are found on the HD gene on Chromosome>40 repeats you develop HD, children 50% chance of developing disease36-39 repeats Grey Zone May develop HD, children may or may not develop HD29-35 repeats the individual will not develop HD, children may

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 functioning of Brain Cells

HD occurs in about 1 out of every 10,000 Caucasian individualsApproximately 2.5 times more individuals are at risk for the disorder because of the midlife peak in age at onsetAbout 40% of those at risk actually have the gene and are too young to exhibit symptomsHD affects males and females equallyHowever the juvenile form of the disease tends to be inherited from fathers

The symptoms are caused by a loss of neurons in the brain that occurs about the time that disease becomes first manifestThe basal ganglia and cortex are ravaged, which can be followed up with a MRI or PETIn the caudate nucleus, populations of enkephalin and substance P containing medium-sized spiny GABAergic projection neurons are the first to be affectedThe 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 Y containing aspiny interneurons are spared by the disease processIt is this characteristic pattern of neuronal cell loss in the basal ganglia that forms the basis for the neurophathological grading of HD

Unique in its GenomeSpans approximately 185 kb (kilobases) in 4p16.3

Comprised of 67 Exons

Directs the Synthesis of two major RNA transcripts

The HD CAG repeat is located in ExonOnly 17 codons from the ATG start of translation

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 link of inherited alleles).

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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 housekeeperNot required for immediate survival and function of the cellIs 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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The mutated Huntingtin in cells follows same pattern as normal proteinThe CAG repeats in the lengthened gene exhibit enhanced reactivity to monoclonal reagents

Produces embryos that fail during gastrulation 7.5 days before they form a nervous system

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 neuronsBut this doesnt explain why neuronal cell types in other regions of the brain 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

Spinal and Bulbar Muscular Atrophy- Causes the progressive loss of anterior horn cells in the spinal cord as well as consequent muscle weakness.

Dentatorubral-Pallidoluysian Atrophy- Results in neuronal cell loss in both the Dentatofugal and Pallidogfugal systems

Spinocerebellar Ataxia- Creates progressive cerebellar ataxia(loss of muscle coordination), muscular atrophy, and a loss of proprioception and vibration sense.

The discovery of the HD Gene along with the understanding of the CAG repeat mutation lead to the understanding and accurate diagnosis of Huntingtons Disease.This improved the clinical management of the diseaseAs scientists discover more information about Huntingtons and the HD mutation, they also grow closer to helping individuals suffering from similar pathogenic processesThe disease process involves pathways common to many cells as well as pathways unique to neuronal cells.The ability to compare numerous disorders caused by the unstable repeat of CAG nucleotides affords promising routes that accelerate the task of overcoming the problems caused by HD (ex: neural cell death)

Presymptomatic Testing: Testing for people who are genetically at risk for getting HD. Confirmatory Testing: Testing that determines whether people who are showing symptoms actually have HD.Prenatal Testing: Testing used to determine whether a fetus is at risk for HD. http://video.on.nytimes.com/?fr_story=d962010d883be3d1278974769d1226cf0ed34933

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Amniocentesis involves testing a sample of amniotic fluid from the womb. Usually done when woman is between 16 and 20 weeks. Chronic Villi Sampling: performed earlier than amniocentesis - between the 10th and 12th weeks of pregnancy. In CVS, a catheter or thin needle is inserted into the womb to extract some of the chorionic villi - cells from the tissue that will become the placenta. The chorionic villi contain the same chromosomes as the fetus.

Usually includes sessions devoted to: genetic counseling, a neurological exam, a psychological interview, discussion of the results, and follow-up.Neurological exam is meant to determine whether the patient has any symptoms, in which case they may choose to discontinue testing procedure. Sessions are meant to ensure that the person about to undergo testing understands the implications of the knowledge 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 a sibling 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 of his/her genetic test for the purpose of confirming the diagnosis.

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Costs vary from center to center.Some centers provide the test for free for patients involved in their studies.Most centers range in price from $600 to $1,500.

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Some insurance providers cover presymptomatic testing.Making a claim could lead to genetic discrimination.Although unusual, it is possible that an insurance company could deny health coverage or cancel an existing policy because of a positive HD test.A positive test result could also be considered a pre-existing condition making it difficult to obtain future health coverage.Most people choose to wait until they get their results, and only seek reimbursement if they dont carry the gene

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Accuracy of a positive or negative test result is almost 100% provided that another family member is known to have the gene for HD.Positive test results cannot predict when the symptoms will begin.Test results should always be confidential.

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Personal relationships may changeReduction of uncertainty Preparation for the future Expenses Emotional trauma Discrimination

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Jeopardy!

Genetics Testing Basic Facts100 100100200200200300300300400400400

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What chromosome is the HD gene located on?Chromosome 4.

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What protein does the functional HD gene produce? Huntingtin.

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How many CAG repeats guarantee HD symptoms?40 repeats.

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What is the specific location of the HD gene?4p16.3

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True or False: patients undergoing presymptomatic testing are not advised to bring a close friend or family member to sessions. False; patients are advised to bring a friend or family member to all sessions unless that person is also at risk for HD.

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Provided that a patient has a family member know to have HD, how accurate is the test for that patient?Almost 100% accurate.

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What are the three types of testing for HD?Presymptomatic, Confirmatory, and Prenatal

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Give three reasons a person at risk for HD may choose not to undergo presymptomatic testing. Discrimination in the workplace, personal relationships may change, emotional trauma, expenses, health insurance, etc.

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What is Chorea?Uncontrollable, dance-like movements of the hands and feet.

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When do the symptoms of HD appear?It depends greatly on the number of repeats occurring in the patients genes.

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What percentage of HD cases are juvenile HD?About 10%.

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What are the three main elements of treatment for Huntingtons?Proper diet and nutrition, exercise, and medication.

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