Introduction
This is a hereditary disease that has slow brain striatum atrophy (Gil and Rego). For several years, a Huntington’s disease patient may go through unrestrained movements, mental impairment and behavioral commotions. Finally, Huntington’s disease patients get totally reliant on a caregiver. The disease is an autosomal dominant condition that affects the equally two genders.
Statistics
The statistics of the Huntington’s disease indicate that out of 100,000 individuals globally, 5 to 10 will have the condition. The disease can attack males and females of every ethnic background (World Health Organization). It is prevalent globally, but, there are geographic regions where it is remarkably common. There are no precise approximations of the number of new incidences every year (Revilla).
Causes
This disease arises as a result of genetic abnormality on chromosome 4, which makes a portion of DNA, known as CAG repeat, to occur more times than expected. Under normal conditions, this DNA section is repeated 10 to 28 times, but in Huntington disease patients, it is repeated 36 to 120 times. The number of repeats grows bigger as the gene is passed to generations. The probability of developing signs increases with the increase in the number of repeat. Hence, as generations inherit the disease, the symptoms appear at younger ages. If one parent is a Huntington disease patient, there is a 50% probability of their child inheriting the gene. If a child inherits the gene from the two parents, the disease will develop at some point in the child’s life, and he or she will pass it on to their children.
Pathology
The most outstanding Huntington disease neuropathology happens within the neostriatum where astrogliosis and selective neuronal loss accompany putamen and caudate nucleus gross atrophy. Marked neural loss is, as well observed in the cerebral cortex deep layers. Other areas, which include thalamus, the globus pallidus, substantia nigra, subthalamic nucleus, as well as cerebellum, demonstrate different levels of atrophy based on the grade of pathology. The degree of neuronal loss, gliosis and gross striatal pathology offers a ground for ranking the severity of Huntington disease pathology (Wexler, Lorimer and Porter).
On grade 0 and 1, there is no observation of gross striatal atrophy. Cases of grade 0 cases lack detectable histologic neuropathology when there is a typical clinical picture, as well as positive history of family indicating Huntington disease. Cases of grade 1 have neuropathologic modifications, which can be microscopically detected though with no gross atrophy. There is the presence of striatal atrophy in grade 2, though the caudate nucleus stays convex. Striatal atrophy is more severe in grade 3, and there is a flat caudate nucleus. Grade 4 has the most severe striatal atrophy with a concave caudate nucleus’ medial surface. The Huntington disease genetic basis is the cysteine-adenosine-guanine repeat expansion, which code for a polyglutamine tract in the huntingtin N-terminus (Ho and Hocaoglu).
The huntingtin function is unknown. It is normally situated in the cytoplasm. The huntingtin association with the cytoplasmic surface of several organelles, which include synaptic vesicles, transport vesicles, mitochondria, and microtubules, increases the likelihood of the normal cellular interactions’ occurrence that may be relevant to neuro-degeneration. The mutant‘s N-terminal fragments accumulate and create inclusions in the nucleus of a cell in the brains of patients with Huntington disease, as well as in several animal and Huntington disease cell models (Loy and McCusker).
The neuronal intranuclear inclusions presence first resulted in the opinion that they are lethal and, thus, pathogenic (Cleret, Fénelon and Benisty). However, recent data propose that neuronal intranuclear inclusions may not be necessary or adequate to result in death of neuronal cell, but translocation into the nucleus is enough to cause death of neuronal cell. Inhibition by caspase in clonal striatal cells demonstrated no link between the decrease in cells aggregates and raised survival (Graham, Deng and Slow). Moreover, postmortem research disclose that neuronal intranuclear inclusions are uncommon in the patients’ striata in comparison to the cortex, and the majority of the aggregates in the striatum are viewed in interneurons’ populations, which characteristically are spared in Huntington patients.
SymptomsThe Huntington’s disease symptoms are mostly apparent in middle age, although this differs from one person to another. As the disease advances, the individual may show behavioral and personality changes, which include irritability, anxiety and depression. Difficulties in memory and cognition also can happen. The most noticeable Huntington’s disease’s symptom is and happens in about 90% of individuals at some point in their sickness (Haddad and Cummings). Chorea comprises of arrhythmic, involuntary motions of the upper and lower appendages, body or face.
Diagnosis
Diagnosis of Huntington’s disease can be done after the physical symptoms appearance. Genetic testing may be employed for confirmation of a physical diagnosis if there is lack of a family history. Even prior to the symptoms onset, genetic testing may affirm if a person or embryo has an amplified trinucleotide repeat copy in the HTT gene, which leads to disease. In spite of pre-symptomatic testing availability, just 5% of the ones at risk of acquiring Huntington’s disease choose to do so (Walker).
Treatment
Huntington disease has no cure, and there exist no way that can stop it from worsening. Treatment is aimed at slowing the symptoms and assisting the patient to function for the longest possible time. Medicine can be prescribed, based on the symptoms. For instance, Dopamine blockers can assist in reducing abnormal conducts and motions. Drugs like tetrabenazine and amantadine are prescribed for extra movement’s control (Goldman and Schafer).
Prognosis
Huntington disease results in disability, which worsens with time. Patients normally die within 15 to 20 years death is frequently caused by infection. Suicide is, as well usual. It is crucial to note that the condition causes different effects on individuals. The number of CAG repeats can ascertain the symptoms severity. Individuals with few repeats can have mild abnormal motions later in life, as well as slow progression of the disease. Persons with a large number of repeats can be affected severely at a young age (Goldman and Schafer).
Prevention
If there is a family history of the condition, genetic counseling is recommended. Genetic counseling for couples with the diseases’ history in the family prior to considering having children is also recommended.
Works Cited
Cleret, de Langavant L, et al. "Awareness of Memory Deficits in Early Stage Huntington's Disease." PLoS One 8.4 (2013): e61676.
Gil, J. M. and A. C. Rego. "Mechanisms of neurodegeneration in Huntington’s disease. ." European Journal of Neuroscience 27.11 (2008): 2803-2820.
Goldman, L. and A. I. Schafer. Goldman’s Cecil Medicine. 24. Philadelphia, Pa: Elsevier Saunders, 2011.
Graham, R. K., et al. "Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin." Cell 125.6 (2006): 1179-91.
Haddad, Monica Santoro and Jeffery L. Cummings. "Huntington’s Disease." Psychiatric Clinics of North America 20.4 (1997): 791-807.
Ho, A. and M. Hocaoglu. "Impact of Huntington's across the entire disease spectrum: the phases and stages of disease from the patient perspective." Clin Genet 80.3 (2011): 235-239.
Loy, C. T. and E. A. McCusker. "Is a motor criterion essential for the diagnosis of clinical huntington disease?" PLoS Curr (2013).
Revilla, Fredy J. Huntington disease. 2011. 7 April 2014. <emedicine.medscape.com/article/1150165-overview#showall>.
Stober, T., W. Wussow and K. Schimrigk. "Bicaudate diameter--the most specific and simple CT parameter in the diagnosis of Huntington's disease." Neuroradiology 26.1 (1984): 25-8.
Walker, F. O. "Huntington's disease." Lancet 369.9557 (2007): 218–28.
Wexler, N. S., et al. "Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset." Proc Natl Acad Sci U S A. 101.10 (2004): 3498-503.
World Health Organization. Genes and human disease: Huntington’s disease. . n.d. 6 April 2014. <www.who.int/genomics/public/geneticdiseases/en/index2.html#HD>.
