INTRODUCTIONTay-Sachs disease or also known as acute infantile variant (Kaback & Desnick, 2011) is a heritabledisorder that mainly affects infants, adolescents and even adults. Thisbasically targets the nervous system of the human body.
It is caused by theabsence of hexosaminidase-A (Hex-A), a vital enzyme found in the brain cellsthat functions in metabolizing certain lipids (Campbell, Reece, Urry, Cain,Wasserman, Minorsky & Jackson, 2015). Without the presence of theseenzymes, the lipid (GM2 ganglioside) accumulates abnormally in cells, specificallyin the nerve cells. After which, the on-going accumulation causes more damageto the brain. Theinheritable disorder commonly starts at early fetal development or during earlystages of pregnancy.
After child birth and up to the point where the childreaches the age of three to six months, he or she ‘appears’ to be normal. Butas soon as the child turns two years older, symptoms of the disease is apparentwherein recurrent seizures and diminishing mental function usually takes place.The child will also be having a hard time crawling, turning over, sitting andeven reaching out (U.S. National Library ofMedicine, 2018). In the worst case scenario, it may lead to blindness,cognitive impairment, paralysis and non-responsiveness. And as soon as the childturns three or four years older, the nervous system becomes badly affected,eventually leading to death.
On the other hand, adults are also susceptible tothis kind of disease merely categorized as the Late-Onset Tay-Sachs disease causing intellectual and neurologicalimpairment (National Human Genome ResearchInstitute, 2011). Becauseof the aforementioned effects of the said disorder and its progressiveobliterations towards the nervous system of the human body, the researcherwrote this study to make the respective readers become aware of this rare andinherited disorder and to let them understand the nature, the causes, theoverall symptoms, the effective management and preventive measures in order topreclude the possible occurrence of this disease. PATHOPHYSIOLOGYAs it is written in the previous section of thepaper, the disease causes fatality common to infants experiencing motor andmental degeneration beforehand and even adults are no exemption to this type ofdisease. It has been discovered and known to experts in the certain field suchas Campbell et al. (2015) that only children inheriting two copies of Tay-Sachsallele (homozygotes) have the disease.
However, the relationship among allelesof a single gene—whether the alleles appear to be completely dominant,incompletely dominant or codominant depend only on the level at which thephenotype is analyzed (organismal, biochemical, and molecular level). Inrelevance to these statements, a certain defect in the Hex-A gene primarilycauses Tay-Sachs disease, wherein humans have two copies of the particulargene. And whether both of these Hex-A genes are active or just either of thetwo, the body will then be able to reproduce or secrete enough enzymes tohinder the irregular building up of the lipids particularly in the brain cells(NHGRI, 2011).
While a person having both active and inactive gene is believedto be a ‘carrier’, he or she is still considered as healthy. But there is afifty percent chance that the disease will be passed on to his or her futureoff-springs—making them potential carriers as well and will have greaterchances of acquiring Tay-Sachs disease coming from their respective parents (ifboth parents happen to be carriers). Mahuran(1999) also presented in his study that Tay-Sachs disease can be primarilycaused by a certain deficiency on any of these proteins such as alpha-(HEXAgene), beta-(HEXB), and GM2 activator protein (GM2A) which eventually leads tostorage of the ganglioside (the lipid), primarily in the lysosomes of neuronalcells.
Inthe study conducted by Utz, Crutcher, Schneider, Sorgen, & Whitley (2014)about the biomarkers of central nervous system inflammation in infantile andjuvenile gangliosidosis, it shows that several associated with inflammationwere elevated in the CSF of infantile gangliosidosis patients, and less so inmore slowly progressing forms of juvenile gangliosidosis, but not in MPSdisease. Also, in a related study done by Jarnes Utz, Kim, King, Ziegler,Schema, Redtree, & Whitley (2017) they were able to map the timeline ofclinical changes evident in patients with infantile gangliosidosis throughprospective evaluation and clinical care. And they have found out that childrenages below 6 months old have hypotonia, children in their first year of agehave severe motor skill impairment while seizures, dysphagia and feeding-tubeplacement are experienced by infants below or before of 18 months of age. CLINICALMANIFESTATION Accordingto USNLM (2018), Tay-Sachs disease is very rare in the general population. Thegenetic mutations that cause this disease are more common in people ofAshkenazi (eastern and central European) Jewish heritage than in those withother backgrounds. It has been said that approximately one in every 27 Jews inthe United States is a carrier of the Tay-Sachs disease gene (NHGRI,2011). Inorder to accomplish the objective of characterizing and determining thecognitive status in a sample of individuals with late-onset GM2 gangliosidosis(commonly referred to as late-onset Tay-Sachs disease), Zaroff, Neudorfer,Morrison, Pastores, Rubin, & Kolodny (2004) evaluated seventeen subjects,ages 18-56 years and were in various stages of disease progression. Thesepatients underwent comprehensive neuropsychological assessment and it came outthat nearly one-half of the sample scored in the impaired range on measures ofprocessing speed, visual sequencing, and set shifting.
One-third of the samplealso scored in the impaired range on measures of delayed verbal recall. Afterthe series of evaluation, researchers concluded that there is a risk ofimpairment in executive functioning and memory as well as cerebellardysfunction among patients diagnosed with late-onset GM2 gangliosidosis. Asidefrom the neuropsychological assessments and the impairments found in adultswith Tay-Sachs disease (Zaroff, et al., 2004),most affected infants have nerve damage starting in the mother’s womb (beforebirth), with symptoms appearing from age 3 to 6 months. Progression is rapid inthis case, and the child will typically pass away by 4 or 5 years old.Additional symptoms of Tay-Sachs among infants include: deafness, progressiveblindness, seizure, muscular stiffness, slow growth, and red spot on the macula(an oval-shaped area near the center of the retina in the eye) (Healthline, 2005).
Internationalefforts and initiatives have been done for early detection and diagnosis suchas the works of Kaback, Lim-Steele, Dabholkar, Brown, Levy, & Zeiger(1993). Their objectives are to provide an update of the internationalexperience with carrier screening and prenatal diagnosis for Tay-Sachs disease(TSD), to assess the impact of these efforts, and to review the recentdevelopments in DNA technology with application to TSD carrier detection andscreening through setting up Tay-Sachs disease testing centers for annualassessments and by doing interventions through Gene product screening (enzymetesting) and DNA-based mutation analysis (in some populations). MEDICALMANAGEMENT Thereare no available medical cures/remedies for the Tay-Sachs disease but certaintreatments such as keeping the child comfortable or the so called ‘palliativecare’ (Healthline, 2005). Palliative caremay include medication for pain (pain killers) in order to ease or soothe thepain of these children by sending pain messages back to their brain through thespecial nerve endings.
Painkilling drugs interfere with these messages, eitherat the site of the injury, in the spinal cord or in the brain itself (Science Museum, 2018). However, there arenumbers of unpleasant side effects associated with painkiller abuse. Mild sideeffects include nausea, vomiting, and diarrhea, usually caused by the way thedrug interacts with opioid receptors along the digestive tract. You can alsoexpect random muscle spasms that occur as a result of the nerves reacting atrandom to various stimuli (Patterson, 2018).Other treatments in minimizing or reducing thenegative effects of the Tay-Sachs disease brought to children and even adultsinclude: anti-epileptics (that are also helpful in controlling seizures),physical therapy, feeding tubes, and respiratory care to reduce mucus buildupin the lungs (Healthline, 2005). PREVENTION Since Tay-Sachs disease is inherited, there is no way toprevent it except through screening.
An individual can screen for carriers ofthe Tay-Sachs disease by doing genetic testing on two parents who are thinkingabout starting a family (NHGRI, 2011). Screening for carriers of Tay-Sachs wasstarted in the 1970s, and has reduced the number of Ashkenazi Jews born withTay-Sachs by 90 percent. ConclusionIn the entirety, Tay-Sachs disease is primarilythe result of deficient amount of the enzyme known as hexosaminidase-A, that is a crucial substance in breaking downlipids or gangliosides. Due to theinsufficient amount of these enzymes, these lipids will otherwise fail tometabolize and will eventually accumulate along the brain cells specifically inthe nerve cells.
The abnormality occurring along the nerve cells will develop duringearly stages of fetal development or during pregnancy and will not be evidentuntil the child reaches three to six months old. Children who are diagnosedwith this type of genetic disorder will only have a shorter life expectancycompared to those children who do not have and will only reach five years atmaximum. Symptoms of motor skills impairment, paralysis, deafness, blindness,loss of muscular strength etc., will be eminent among infants and evenjuveniles who have TSDs. Even so, adults are also susceptible to this type ofgenetic disorder leading to neuropsychological degeneration and is consideredas the Late Onset Tay-Sachs disease. Nofound cures are available at this point in time but several treatments areavailable such as the usage of pain killers, anti-epileptic drugs, and physicaltherapies.
But some of these medications and medical practices should be takeninto careful account since these do not only have beneficial effects butnegative effects on the subject as well. Lastly,the best way to prevent the rapid spread and progression of this disease amongindividuals and particularly, infants is to have their parents checked ortested with genetic tests or even simple blood tests that detect genes havingTay-Sachs disease and therefore, reducing the chances of pass ing on theinactive gene having lesser amounts of Hex-A to their offspring.