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Comments - Tay Sachs disease

2020-06-24 来源: 51Due教员组 类别: 更多范文


下面为大家整理一篇优秀的essay代写范文 -- Comments - Tay Sachs disease,文章讲述Tay-Sachs病,即所谓的GM2神经节苷脂病,是一种罕见的严重的常染色体隐性神经退行性疾病,由大脑中GM2神经节苷脂的水解功能障碍引起。当致命数量的GM2神经节苷脂(细胞膜成分)堆积在组织和神经细胞中时,该疾病就会因神经细胞过早死亡而发生。 Tay-Sachs疾病的特征是在第一岁时出现快速的精神和身体退化,并在大多数情况下最终在2-4年内导致死亡。


Comments - Tay Sachs disease

Tay-Sachs disease, so called GM2 gangliosidosis, is a rare and severe autosomal recessive neurodegenerative disorder caused by dysfunction of hydrolysis of GM2 ganglioside in the brain. When fatal amount of GM2 gangliosides, the cell membrane components, accumulate in the tissue and nerve cells, the disease occurs by the premature death of nerve cells. Tay-Sachs disease is characterized by rapid mental and physical deterioration occurring in the first year of age and eventually leading to death in 2-4 years in most of situation.


The disease is named after the two scientists. One is the British ophthalmologist Waren Tay who is the first one to mention a symptom that cherry red spot presenting in the retina of the eye (Waren 55), and the other one is American neurologist Bernard Sachs who demonstrated the change in cellular level of Tay-Sachs disease and found the high occurrence rate of this disease in Ashkenazi Jewish population.(Fernandes Filho and Shapiro) In early 20th century, researches stated that this disorder resulting from a genetic mutation of the HEXA gene which encoding the alpha subunit of β-hexosaminidase A. As β-hexosaminidase A is a lisosomal enzyme participating in the enzymic hydrolysis of GM2, the genetic mutation of enzyme leads to the deficiency of enzyme thereby resulting excessive amount of GM2 in the cells.( Li, S C,, et al. 254)


Tay-Sachs disease performs in several forms based on the age of onset: Infantile Tay-Sachs disease or Late-Onset Tay-Sachs disease. Different onsets may rely on diverse mutations in the HEXA gene. Classic infantile Tay-Sachs disease is a fatal autosomal recessive disorder which results from inheriting two Tay-Sachs alleles from both parents, while late-onset forms occur by various mutation bases. Most of patients with classic infantile Tay-Sachs disease perform normally at new born age, while the clinical symptoms appear in postnatal three or six months. Initially pediatric patients show exaggerated startle reaction to stimulus such as sound, light and touch, and generally develop into irritability and seizures along with vision and hearing loss, amentia and paralysis. Around 6-month age, an eye abnormality named cherry-red spot in retina which can be identified via eye examination contributing to make a diagnosis of this disease. The frequency and severity of seizure also increase, which can appear as generalized tonic clonic seizure or myoclonic one. The course of disease normally ranged from six to eight months. Pediatric patients normally die of aspiration pneumonia or other secondary infection. Late- onset Tay-Sachs disease is a rare form compared with the infantile one, which can occur during adolescence and adulthood. People with this form may potentially be heterozygous carriers, the one who inherit only one mutant allele and still able to function hexosaminidase A activity in some extent. In contract to the infantile form, late-onset form is usually not fatal. Physical problems such as difficulty on speech, gait and keeping balance are normally seen in patients. (Neudorfer, O, et al 119) Psychotic episodes are also found in these patients. In most cases, diagnosis was delayed or missed.


Up to this day, there is no proper treatment for Tay-Sachs disease. Accurate diagnosis is the best way to prevent or reduce the morbidity of Tay-Sachs. Three main methods have been used to achieve the goal. First of all, preconception screening is recommended when people are planning to build a family. Two main populations are facing high risk on containing the mutant allele which may lead to the condition: people of Ashkenazi Jewish descent and people with known family medical history of Tay-Sachs. Blood sampling is performed to test the HEXA mutation. If both couples are HEXA mutant carriers, the offspring has 25% chance to develop Tay-Sachs (seen figure 1). In this case, prenatal diagnosis is essential to give a birth to healthy child. Chronic villus sampling is the most common approach taken for screening where cell sampling from placenta and genetic examination are performed between weeks 11 and 14 of pregnancy. Amniocentesis is the other approach which normally performed at weeks 15 to 18 via using a needle to collect amniotic fluid for testing. Once the confirmation of Tay-Sachs disease is done, patients should make a decision on terminate or continue the pregnancy. The third option is preimplantation genetic diagnosis (PGD). In vitro fertilization (IVF) has been used in PGD, where unfertilized eggs are collected from ovaries and finished the fertilization process with sperm under the laboratory condition. After few days of incubation period, screening in resulting embryos for Tay-Sachs disease is performed. No more than two healthy embryos can be transferred back into the uterus for further development.(Andrews LB et.al.


Figure 1. Tay-Sachs disease is an autosomal recessive neurodegenerative disorder. Figure 2 shows the probability for offspring to develop Tay-Sachs disease.






Numerous researches have been performed aiming in various directions; however, few of them can be effective to treat the Tay-Sachs disease. Enzyme replacement therapy was considered as potential technique to treat lysosomal storage disease, but the size of HEXA enzyme is too large to permeate the blood brain barrier; therefore it is impossible to directly apply the replacement therapy through blood vessels. Investigators also considered substrate reduction therapy as another experimental approach. The level of sialidase was increased which led to huge reduction in the amount of GM2. The result may lighten a way to develop a safe pharmacological approach in treating Tay-Sachs disease (Suleiman 1111). For patients with late-onset Tay-Sachs disease, the ability of β-hexosaminidase A remains in some extent and deteriorates in a relatively slow tempo, so increasing the ability may be one of the potential therapies. However, there is no known treatment or medical product could increase the amount of β-hexosaminidase A into sufficient level.











Work Cited

Tay, Waren (1881), "Symmetrical changes in the region of the yellow spot in each eye of an infant", Transactions of the Ophthalmological Society 1: 55–57

Igdoura, Suleiman A., et al. "Sialidase-Mediated Depletion of Gm2 Ganglioside in Tay-Sachs Neuroglia Cells." Human Molecular Genetics 8.6 (1999): 1111-16.

Neudorfer, O, et al. "Late-Onset Tay-Sachs Disease: Phenotypic Characterization and Genotypic    Correlation in 21 Affected Patients." Genetics in Medicine 7.2 (2005): 119-23.

Li, S C,, et al. "Evidence for the presence of two separate protein activators for the enzymic hydrolysis of GM1 and GM2 gangliosides." Journal of Biological Chemistry 254.21(1979):10592-5.

Fernandes Filho, J., and B. E. Shapiro. "Tay-Sachs Disease."Archives of Neurology 61.9 (2004): 1466-68. Print.

Andrews LB, Fullarton JE, Holtzman NA, et al., editors. Assessing Genetic Risks: Implications for Health and Social Policy.Washington (DC): National Academies Press (US); 1994.



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