Tay-Sachs Disease
Tay-Sachs Disease is a neurological disorder that is passed on from parent to child in the same way that other genetic traits are passed on. The first section of this paper, on pathophysiology, will go into this subject further. It will explain not only how the trait for this disease is passed from generation to generation, but also the specific mutations that cause it. This section will explore the trait that is expressed when the gene is turned on, how it effects cell metabolism, and in turn, the disorder that is caused in the body as a result. The second section will describe the clinical manifestation of the disease. It will cover what is typical in a patient with the disease, initial and continuing symptomology, and unfortunately, the cause of death in most people who have the disease. Lastly, the final section will reveal the medical management of the disease. Tay-Sachs has caused so much suffering, but with the advances made in genetic technology, and a little luck, the current generation of researchers are hoping to change that (Wise, 2012).
Pathophysiology
Tay-Sachs disease results from a number of different mutations on the fifteenth chromosome. When the gene functions correctly, it results in an enzyme called hexosaminodase. This enzyme breaks down molecules in the body called gangliosides. Without the proper enzyme to break these molecules down, they build up in what are called ganglion cells. These cells then swell keeping the neurons fro functioning properly. This effects the neurological system in many terrible ways, which will be explored further in the Clinical Manifestation section (Kaback, 2013).
“Nearly 130 mutations have been reported so far in the HEXA gene to cause TSD” (Mistri 2012). There are small deletion mutations, resulting in a frameshift in the mRNA. That means that all of the codons in the entire gene, which fall after the beginning of the frame shift, are off by one or more base pairs. That changes every codon, resulting in an entire chain of the wrong amino acids. There are also single base substitutions, duplications, and insertions, all of which result in a single defective codon, which in turn results in single incorrect amino acid in the resulting peptide. Unfortunately, it only takes one incorrect amino acid to render the enzyme inoperable. (Mistri 2012).
The disease is named for Warren Tay (1823-1927) and Bernard Sachs (1858-1954). Tay was an ophthalmologist who described the cherry red spot on the retina of the eye which is a sure sign of Tay-Sachs in 1881. Sachs was a neurologist who was the first to describe the cellular changes which result from the disease, and observed the inheritance of the disease through family lines several years after Tay described his patient (NTSAD).
Clinical Manifestation
Most babies who are born with the disease seem completely normal for their first 3-6 months of life. In it's classic infantile form, this is the age at which his muscles begin to atrophy, causing motor weakness. As the muscles degenerate he starts suffering from muscle twitches caused by sudden contractions of the muscles called myoclonic jerks, and his physical reaction to sharp noises becomes exaggerated. At some point he will stop being able to learn new motor skills, and lose the ability to display the motor skills he's already learned. By the age of two his nervous system will be so degenerated that he is most likely paralyzed, with little to no muscle movement at all. Recurring seizures often prove fatal. He will likely die by the age of 5. (Kaback, 1999).
In it's juvenile form symptoms usually first appear between the ages of two and five. Slurred speech, muscle cramps and difficulty swallowing are among the first signs. Eventually she will lose her ability to communicate and walk and becomes increasingly prone to respiratory infections. The disease progresses in a similar fashion classic infantile Tay-Sachs, but the “earlier the first signs are observed, the more quickly the disease will progress” (NTSAD).
The last form o the disease is late-onset form. About 40% of late-onset adults experience mental health problems at the first sings of the disease. This unfortunately often leads to difficulty in diagnosis. Adults tend to experience a very slow loss of motor skills which may or may not eventually lead to the seizures that are experienced by children with classic-infantile and juvenile forms. (NTSAD).
Medical Management
There is currently no treatment of the disease itself, only treatment for it's various symptoms. This section will focus on prevention and the current research into a cure. The three main options for prevention are prenatal diagnosis, pre-implantation genetic diagnosis, and donor selection. Testing is key in all of these options (Ainsworth, 2011).
In prenatal diagnosis, the fetus is tested in-vitro. This is an invasive procedure that involves removing a piece of the placenta. The testing alone has the potential to be harmful to the child, so the decision to test is often a difficult one. This method of prevention is fraught with moral quandary. Once a test has proven positive, the couple then has the option to terminate the pregnancy (Ainsworth, 2011). In a journal called The Future of Children, Paul Wise said, l
“The use of prenatal diagnostic technology is also characterized by significant social disparities, particularly when complex medical procedures or delivery infrastructures are required.' Yet, the continued link of prenatal diagnosis to pregnancy termination has made the disparate use of prenatal screening hard to interpret. Social differences in the acceptability of abortion and in access to abortion could also be contributing to observed disparities in the use of prenatal diagnostic procedures” (2012).
The second option is pre-implantation genetic diagnosis. When a couple who have been tested, who know that they are both carriers of this disease chooses to reproduce, they have the option of using in-vitro fertilization and having each embryo tested before implantation. This allows the parents to discard any embryos who would eventually develop the disease before the eggs have ever been implanted in the uterus. (Ainsworth, 2011). Those who have moral difficulty in pregnancy termination, for some reason, usually don't have any problem with this option.
The last option is the simplest. If a person is a carrier, he or she can choose not to reproduce with someone else who is also a carrier. If two people who wish to reproduce know that they are both carriers, they can seek either egg or sperm donation from a party who is not a carrier. This will prevent the child from having the disease. In populations in which the disease is most common, such as the Ashkenazi Jews (Haghighi, 2011), testing is common, so it is also possible to specifically choose a mate based on their carrier status (Ainsworth, 2011).
As for research, each day brings more advances which may someday lead to treatment or even a cure. Gene therapy, which is an attempt to correct the mutations in the genetic code, has been accomplished in cats and mice, and researchers are currently putting together a package for human trials to be submitted to the FDA. The FDA has yet to ever approve any kind of gene therapy for release to the public, though, so it may prove difficult to get this method much further than the research phase. Researchers are also looking into molecular chaperones. These are tiny molecules that are able to enter the brain and the central nervous system to impact the defective hexoaminodase enzymes . “These chaperones attach to an inactive enzyme so that it takes the correct functional shape.” This treatment is only effective in cases of late-onset, and is still only in it's infancy. Substrate inhibition is one of the avenues of research that have come the farthest. This focuses on the use of small molecules that slow the accumulation of gangliosides in the nervous system. They can't stop the accumulation, though, which puts this in the cagtegory of treatment instead of cure. The last two research approaches are those of stem cells and bone marrow transplant. Bone marrow transplant is extremely invasive, and stem cell research is challenged at every turn by those who see it as a morally deplorable activity, so these two plan of attack face significant challenges (NTSAD).
Conclusion
Fucking hell I'm tired. I'll write the conclusion later...