On each individual. Juvenile Huntington’s Disease differs

On the daily basis we frequent people with all kinds of diseases. From tumors to cancers. The minimal thing can be impacting to a person’s life.

Such as that of Huntington’s diseases. Huntington’s disease is an inherited disorder that is resulted in death of brain cells. As the disease progresses, unplanned, body movements become more obvious. This fact raises several ethical debates. The debate to which should the parents of the child/newborn have the right to test the child or should the human being decide when to get tested for this specific disease. Complications such as pneumonia, heart disease, and physical injury reduce life expectancy. In the early stages of the disease, there are multiple changes in personality, cognition, and physical skills.

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Symptoms are generally not severe enough to be recognized on their own at the earlier stages.The changes might even be minimal and most people consider it as normal.The most frequent initial physical symptoms are jerky, random, and uncontrollable movements called chorea. These are signs that the system in the brain that is responsible for movement has been affected. Psychomotor functions become increasingly impaired, such that any action that requires muscle control is affected. Common consequences are physical instability, abnormal facial expression, and difficulty chewing, swallowing, and speaking. Another symptom could also be sleep.

The symptoms vary depending on each individual. Juvenile Huntington’s Disease differs from these symptoms in that it generally progresses faster and chorea is exhibited, if at all, with rigidity being the dominant symptom. Seizures are also a common symptom of this form of HD. Difficulties in recognizing other people’s negative expressions have also been observed. Most of the time it is family members that realize that something is wrong with that specific person.Mutant Huntingtin is expressed throughout the body and associated with abnormalities in peripheral tissues that are directly caused by such expression outside the brain. These abnormalities include muscle atrophy, cardiac failure, impaired glucose tolerance, weight loss, osteoporosis, and testicular atrophy.All humans have two copies of the Huntingtin gene, which codes for the protein Huntingtin.

The gene is also called HD and IT15, which stands for ‘interesting transcript 15’. Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change length between generations. If the repeat is present in a healthy gene, a dynamic mutation may increase the repeat count and result in a defective gene. When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant Huntingtin protein .

The differing functions of these proteins are the cause of pathological changes which in turn cause the disease symptoms. The Huntington’s disease mutation is genetically dominant and almost fully penetrant: mutation of either of a person’s HTT alleles causes the disease. It is not inherited according to sex, but the length of the repeated section of the gene its severity can be influenced by the sex of the affected father or mother.

HD is one of several trinucleotide repeat disorders which are caused by the length of a repeated section of a gene exceeding a normal range. The HTT gene is located on the short arm of chromosome 4. Classification of the trinucleotide repeat, and resulting disease status, depends on the number of CAG repeats. With very large repeat counts, HD has full penetrance and can occur under the age of 20, when it is then referred to as juvenile HD, akinetic-rigid, or Westphal variant HD. This accounts for about 7% of HD carriers.Huntington’s disease has autosomal dominant inheritance, meaning that an affected individual typically inherits one copy of the gene with an expanded trinucleotide repeat  from an affected parent. Trinucleotide CAG repeats over 28 are unstable during replication, and this instability increases with the number of repeats present. It is rare for Huntington’s disease to be caused by a new mutation, where neither parent has over 36 CAG repeats.

In the rare situations where both parents have an expanded HD gene, the risk increases to 75%, and when either parent has two expanded copies, the risk is 100% . Individuals with both genes affected are rare. For some time HD was thought to be the only disease for which possession of a second mutated gene did not affect symptoms and progression, but it has since been found that it can affect the phenotype and the rate of progression. The huntingtin protein interacts with over 100 other proteins, and appears to have multiple biological functions.

The behavior of this mutated protein is not completely understood, but it is toxic to certain cell types, particularly in the brain. Early damage is most evident in the striatum, but as the disease progresses, other areas of the brain are also more conspicuously affected. Early symptoms are attributable to functions of the striatum and its cortical connections—namely control over movement, mood and higher cognitive function.HTT is expressed in all mammalian cells. The highest concentrations are found in the brain and testes, with moderate amounts in the liver, heart, and lungs.

In animals genetically modified to exhibit HD, several functions of HTT have been found. In these animals, HTT is important for embryonic development, as its absence is related to embryonic death. Caspase, an enzyme which plays a role in catalyzing apoptosis, is thought to be activated by the mutated gene through damaging the ubiquitin-protease system. It also acts as an anti-apoptotic agent preventing programmed cell death and controls the production of brain-derived neurotrophic factor, a protein which protects neurons and regulates their creation during neurogenesis. HTT also facilitates vesicular transport and synaptic transmission and controls neuronal gene transcription.

In its mutant  form, the protein is more prone to cleavage that creates shorter fragments containing the polyglutamine expansion. These aggregates share the same fundamental cross-? amyloid architecture seen in other protein deposition diseases. Over time, the aggregates accumulate to form inclusion bodies within cells, ultimately interfering with neuron function. Embryos produced using in vitro fertilization may be genetically tested for HD using preimplantation genetic diagnosis . This technique, where one or two cells are extracted from a typically 4- to 8-cell embryo and then tested for the genetic abnormality, can then be used to ensure embryos affected with HD genes are not implanted, and therefore any offspring will not inherit the disease.

Some forms of preimplantation genetic diagnosis—non-disclosure or exclusion testing—allow at-risk people to have HD-free offspring without revealing their own parental genotype, giving no information about whether they themselves are destined to develop HD. In exclusion testing, the embryos’ DNA is compared with that of the parents and grandparents to avoid inheritance of the chromosomal region containing the HD gene from the affected grandparent. In non-disclosure testing, only disease-free embryos are replaced in the uterus while the parental genotype and hence parental risk for HD are never disclosed.Prenatal testing   It is also possible to obtain a prenatal diagnosis for an embryo or fetus in the womb, using fetal genetic material acquired through chorionic villus sampling. An amniocentesis can be performed if the pregnancy is further along, within 14–18 weeks.

This procedure looks at the amniotic fluid surrounding the baby for indicators of the HD mutation. This, too, can be paired with exclusion testing to avoid disclosure of parental genotype. Prenatal testing can be done when a parent has been diagnosed with HD, when they have had genetic testing showing the expansion of the HTT gene, or when they have a 50% chance of inheriting the disease. The parents can be counseled on their options, which include termination of pregnancy, and on the difficulties of a child with the identified gene.

In addition, in at-risk pregnancies due to an affected male partner, non-invasive prenatal diagnosis can be performed by analyzing cell-free fetal DNA in a blood sample taken from the mother  between six and twelve weeks of pregnancy. There is no cure for HD, but there are treatments available to reduce the severity of some of its symptoms. For many of these treatments, evidence to confirm their effectiveness in treating symptoms of HD specifically are incomplete. As the disease progresses the ability to care for oneself declines, and carefully managed multidisciplinary caregiving becomes increasingly necessary. Making nutrition management decisions is extremely important as the disease progresses. Assessment and management by speech-language pathologists with experience in Huntington’s disease is recommended. Goals of early rehabilitation interventions are prevention of loss of function.

Participation in rehabilitation programs during early to middle stage of the disease may be beneficial as it translates into long term maintenance of motor and functional performance. Rehabilitation during the late stage aims to compensate for motor and functional losses.


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