AmyotrophicLateral Sclerosis (ALS)
GenericTesting and counseling can be used to ascertain the probability ofhaving familial ALS.
Thesis:people who have had relatives suffering from ALS should undergogenetic testing and counseling to ascertain whether there is aprobability of them suffering ALS in their 40s to 70s.
A.Definition of ALS
B.Types of ALS
A.Research findings on familial ALS.
B.Genes and mutations in familial ALS
C.Patterns of inheritance
IV.Genetic counseling and testing
Consequences of genetic counseling and testing
C.Prevention rates with early detection of ALS gene mutations.
Amyotrophiclateral sclerosis (ALS) is a very severe neurodegenerative disease.Its etiology is unknown and it is characterized by paralysis thatprogresses rapidly. After 3-5 years of onset of symptoms, it cancause death because of respiratory failure (Genet sec.1). ALS has aneffect on the motor neurons, that is, special nerve cells importantin controlling the strength and coordinating the movement of muscles.When the human body suffers ALS, there is death of the motor neurons.This disease is not curable and results in difficulty in coordinatingmovement of the body muscles-ataxia as well as the mental ability tofunction-dementia (JPND research sec.1). It is important to note thatnerve cells cannot regenerate after destruction. Pathophysiologycategorizes ALS into two categories depending on the cause, that is,familial ALS and sporadic ALS. 90-95% of ALS is sporadic. This meansthat the cause is unknown (ALS Association par.1).
Disordersof the nervous are classified among the most severe problems ofhealth which face the society in the modern day world. Some of thesenervous system conditions such as familial ALS and Huntington’sdisease have clear causes which are genetic. However, others developas a result of complex interactions between environmental as well asgenetic influences which are likely to affect the central nervoussystem in quite a number of ways (McGovern Institute for BrainResearch sec. 2&3). There is a twist that happens in the life ofa person after diagnosis with an illness like ALS. In instances wherethe client is well informed, they know what they expect to happen totheir ability to function as the disease process progresses. Geneticresearch has identified 5-10% inheritance rates in family lines.Therefore, as people take care of their ailing relatives, they livewith the suspicion that the same scenario may happen to them in their40s to 70s. This research article aims to find out whether genetictesting and counseling can be used to ascertain the probability ofsomeone suffering ALS when they have had relatives who have sufferedALS.
I. Neurodegenerative diseases
Neurodegenerativedisease, also known as degenerative nerve disease, is a broadterminology which refers to conditions which affect the human brainspecifically the neurons. Neurodegeneration is a major aspect in manydiseases that are categorized under degenerative diseases.Neurodegeneration is coined from two words that is, “neuro” whichmeans the cells of the nerve and “degeneration” which meansdamage that is progressive. Therefore, the term Neurodegeneration isused in a variety of conditions that lead to loss of structure aswell as function of the nerves (Robertson sec. 1). The neuron is thebasic functional unit of the nervous system and do not replacethemselves. This means that when the neurons are damaged, they dieand no process in the body can make them regenerate (JPND researchpar. 1&2). Neurodegenerative diseases affect many body activitiesincluding body balance, heart functioning, breathing and talking.Examples of neurodegenerative diseases are, Parkinson’s disease,Friedrieich’s ataxia, Huntington’s disease, Lewy body disease,Alzeimer’s disease, spinal muscular atrophy and Amyotrophic lateralsclerosis-ALS. As mentioned above, there are quite a number ofchanges that happen in the body as a result of Neurodegeneration.These are inclusive loss in the cognitive ability, that is, memoryand decision making.
II.Amyotrophic lateral sclerosis
ALSaffects nerve cells specialized to control the movement and strengthof muscles (Genetics Home Reference sec. 1). Degeneration of thenerves located in the spinal cord, that is, lower motor neurons,results in deterioration in muscle movement because of muscleatrophy. On the other hand, degeneration of the motor neurons in thebrain causes cognitive impairment due to damage of prefrontalneurons. When someone suffers ALS, there is deterioration of motorneurons that reach to the spinal cord from the brain. Once neuronsresponsible for controlling body mobility die, there is loss ofability to control the movement of the muscles by the brain. Due toprogressive degeneration in the motor neurons, ALS patients may beleft paralyzed completely in the latter stages of the disease(University of Cincinnati sec.2&3).
B.Types of ALS
Thereare two classical ways that have been used to distinguish the typesof ALS, that is, a family history that is positive for ALS and ALSwhich occurs without evidence of other family cases.
Thisaccounts for 90-95% of ALS. A sporadically occurring disease processis one which occurs in absence of a family history. There are certainfactors that have been linked to sporadic ALS but do not cause thedisease. These include oxidative stress, dysfunction of themitochondria, glutamate toxicity, immune system abnormalities andtoxic exposures (Muscular Dystrophy Association sec.1).
Onmany occasions, juvenile ALS is genetic and could be inherited in afashion that is autosomal recessive or autosomal dominant. Unlikeother types of ALS whose signs and symptoms manifest between ages 40and 70, juvenile ALS presents its signs and symptoms by the age of 25years or even younger. Also, the symptoms of juvenile ALS are notrapidly progressing as compared to the other types of ALS. Peoplewith this type of ALS have a life expectancy that is normal (Geneticand Rare Diseases Information Center par.1).
Thistype of ALS accounts for 5-10% and often arises in families whichhave a history of ALS just as the name suggests. There are genes thathave been mapped to specific chromosome regions associated with ALS.This is the main area of focus for this paper and more will bediscussed in the next section (Muscular Dystrophy Association sec.7).
III.Familial ALS (FALS)
A.Research finding on familial ALS
Genemutations responsible for FALS have continued to be uncovered overthe years. There are quite interesting research findings documentedon FALS. Every year in the United States of America, 5000 people arediagnosed with ALS. Over a given time, 30,000 people live with ALS.There are more than thirteen genes that have been identified ascauses of FALS with the three commonest being: TAR DNA bindingprotein (TDP43 or TARDBP), superoxide dismutase 1(SORD1) and fused insarcoma (FUS). Out of all the cases of FALS diagnosed, 20% are due tomutations in the gene ALS1/SOD1. As pertains to this fact, it isimportant to note that in association to FALS, the mutations in SOD1are more than 100. After the onset of symptoms for FALS, there is anaverage time for survival of around two to three years, 20% of thepopulation survives for a period of approximately five years whileten percent of the population survives for up to ten years (MuscularDystrophy Association sec.2).
B.Genes and mutations in familial ALS
Genesassociated with FALS contribute largely in neuronal function or couldas well be involved in production of a variety of proteins. However,it still remains unclear how gene mutations related to FALS result inthe damage and subsequent death of the motor neurons. Majority of themotor neurons that are affected in the Pathophysiology of FALSusually have protein aggregate build up. It is however unknown if theaggregates cause ALS, or whether FALS is caused by the by product ofthe cell that is dying. Below, are the genes identified to cause FALSwhen mutations occur:
1.C9orf72-this gene is responsible for thirty to forty percent of FALS inEurope and the United States of America. Mutations in this genedecreases the normal amount of C9orf72 protein thus production ofaltered protein which interferes with functionality of the cell(Genetics Home Reference sec. 3).
2.SOD1(superoxide dismutase 1) – as mentioned above, this accounts fortwenty percent of all the cases of FALS diagnosed. This is becausethere are about 170 mutations in the gene SOD1 that have beenidentified to cause ALS. SOD1 is thought to probably acquire new andharmful properties when mutations occur. The motor neurons are verysensitive to alterations in SOD1. However the cause of this extremesensitivity has not been documented (Genetics Home Reference sec. 3).
3.TARDBP(TAR DNA Binding Protein) – this gene mutation is a cause in about 5%of the cases diagnosed. This gene is expressed during the process oforganogenesis in pregnancy. 50 mutations of this gene cause ALS.Mutations in this gene are thought to affect the section of theprotein that is involved in the manufacture of RNA (Genetics HomeReference sec. 3).
4.FUS(FUS RNA Binding protein)- it is a cause in about 5% of the casesdiagnosed for ALS. There are about 50 mutations for this gene thatare known to cause ALS. Most of the changes caused by the genemutations alter the protein areas that are involved in the binding ofDNA as well as the processing of mRNA. For this mutation, individualstend to exhibit the symptoms earlier and compared to people withother types of gene mutations, their life expectancy is reduced(Genetics Home Reference sec.3).
5.ANG(Angiogenin ribonuclease) – Mutations in this gene account for onepercent of all cases diagnosed. This gene issues instructions for themanufacture of protein angiogenin. Mutations in this gene result in areduction in the angiogenin activity. As a result, there isinactivity of rRNA and a negative impact on cells that may cause themto die in the long run (Genetics Home Reference sec.3).
6.ALS2(alsin Rho guanine nucleotide exchange factor) – the proteinsresponsible for the production of this gene are found in largeamounts in the motor neurons. There are at least 8 mutations that areknown to cause ALS. There is deletion of a single nucleotide buildingblock of the DNA in the gene which results in alteration ofinstructions that are necessary for the formation of proteins forgene formation (Genetics Home Reference sec.3).
7.SETX(senataxin) – it is produced in the muscles, brain and spinal cord.The mutations which occur in SETX alter the shape of the gene andmost of the time results in juvenile ALS. It is however unclear howthis occurs (Genetics Home Reference sec.3).
8.VAPB(vesicle associated membrane protein)- there are two gene mutationswhich occur in this gene that result in ALS. In both mutations, thereis production of abnormal VAPB proteins which are unable to activatea response to unfold the proteins. Because of this, aggregates areformed from the abnormal proteins which lead to death (Genetics HomeReference sec. 3).
C.Patterns of Inheritance
Genesusually present in pairs because one copy is obtained from anindividual parent. For the genes responsible to cause ALS, one copythat has undergone mutation is capable to cause the disease. This isknown as the “dominant” gene. For other patterns of inheritanceinvolved in other disease types, the two copies of the gene must haveundergone the mutation for the disease to occur. This is known as the“recessive” gene. In the process of formation of the sperm andegg, the pairs of the gene split so that a sperm (or even the egg) onhas a single copy of the gene. When one of the parents has the genemutations for ALS, there is always a 50-50 probability of the diseasegene being passed on to one of the children. In a scenario where thegene is dominant, then the child will probably develop ALS. However,if the gene is recessive, the child would have to acquire two diseasegenes, one inherited from every parent. If the two parents have asingle copy of the gene, there is a 25% chance of one childinheriting the two copies and having ALS (ALS Association sec.3).
IV.Genetic counseling and testing
Geneticcounseling is important if there is greater than one person in yourfamily who have suffered ALS. This will help to do an evaluation ofthe risks as well as hold a discussion on the consequences of genetictesting. A genetic counselor helps the client in working through theadvantages and disadvantages of genetic testing on the basis of theirvalues. Genetic counseling does not always result in genetic testing.Genetic testing on the other hand involves collection of either asaliva or blood sample in a special tube. The sample is then taken tothe lab for checking of evidence of any abnormal genes. Results canbe ready after a few weeks or months (ALS Association sec. 2 &3).
Consequence of genetic counseling and testing
Duringthe process of identifying the mutations that are responsible tocause ALS, there are quite a number of effects of this procedure onthe family members. This is because all the biological members of thefamily could be at risk of processing the genes mutations responsiblefor ALS.
Soas to carry out the test, individuals have different reasons fordeciding to have the genetic test performed for them. Quite a numberof reasons have been identified and they are as stated below:
For reproductive as well as future planning
Reduction of anxiety
Contributions to researches
To acquire knowledge that may benefit the relatives and off springs
To obtain baseline information for lifestyle adjustments
Dueto differences in personalities and interests in the society, someindividuals may not want to have the test conducted on them despitethem having first degree relatives who have succumbed to ALS. Reasonsfor refusal of the test may include:
Difficulty in facing the outcome of the test, that is, the risk of having the disease in future.
A wish to maintain some degree of hope that no one will acquire the disease despite their parents having it.
A desire to spare their very close friends as well as relatives from worrying incase the outcome of the test is positive (Chio et al 480).
Belowis a description of the psychological and social consequences ofgenetic counseling and testing.
Whenthere is evidence of first degree relatives having suffered ALS,there is usually a lot of uncertainty involved concerning thepredictivity of the test results. Sometimes, when the individual isnot well informed concerning the test as well as the disease process,they may suffer psychological stress due to over thinking on whatwill transpire during the test as well as the results. For subjectswho test positive, they will suffer psychological stress that isrelated to the different attitudes they will experience as pertainsto sharing of the information with the family members and otherrelatives (Chio et al 480)
Afterone has had a test conducted and they test positive, there are quitea number of aspects regarding their lives that changes. This isbecause, they have an inner voice inside them that keeps remindingthem of the fact that they will be a burden to their relatives aswell as close relatives when the disease process sets in. There isalso fear of abandonment in nursing homes by their relatives whenthey cannot tolerate taking care of them any more due to theincapacitating disease process. There are severe forms of rejectionand estrangement associated with testing positive that people facelike being viewed as a parent or partner who is less than ideal. Theymay also face discrimination in health or life insurance policies,work places, during adoption or when seeking higher levels ofeducation.
Testingpositive is not the only outcome that may worry individuals. Testingnegative is also an issue of concern for other individuals. There isa concept referred to as the survivor guilt, in that, an individualexperiences feelings of isolation as well as estrangement to sensesof guilt toward relatives who turned out positive.
Theethical legal implications of genetic testing and counseling include:informed consent and information, rights of professionals as well asthe patients, right to get tested or not, responsibility of theindividual to share the information with relatives who are at risk,privacy and confidentiality, the risk of being discriminated,consequences of diagnosis prenatally. The issues of ethical legalimplications have been studied widely but in a different context,that is, susceptibility to cancer. They continue to undergo analysisbecause genetic testing has become increasingly complex and common(Chio et al 480).
Prevention rates with early detection of ALS gene mutations.
Individualswho are carriers of gene mutations, especially those of SOD1, couldwish to so that they can make life decisions like marriage. However,it may be extremely tough living with knowledge of the presence ofthe gene mutation. Up to date, ALS can neither be cured nor prevented(Amyotrophic Lateral Sclerosis Society of Canada). No medicationshave been proven to reverse, stop or prevent ALS. However, there aremedications that can be used to slow the progression of the disease.This can help to prolong the life expectancy period on an individualby about three months (Wedemeyer sec. 13).
Fromthe above two authors, it is clear that there is no cure for ALSneither can it be prevented. However, one of the authors states thatearly diagnosis can help to slow down the symptoms. Genetic testingand counseling should be highly encouraged for people who have ALSrunning in their families as it may help to extend their lifeexpectancy as well as increase their years of productivity. Afterweighing the pros and cons of genetic testing and counseling, itclearly comes out that clients are most likely to benefit byundergoing genetic counseling prior to having the test. This isbecause they get empowered by getting sufficient information toenable them make decisions. This will also help to minimize theanxiety and stress related to having the test.
Thispaper sought to find out whether genetic testing and counseling canhelp to prevent ALS in individuals who have relatives who sufferedALS. It explored quite a number of areas in detail. From thefindings, it is evident that early diagnosis that one has genemutations linked with ALS does not make it possible to cure orprevent ALS. However, genetic testing and counseling is encouragedbecause it helps to slow the symptoms thus increasing years ofproductivity besides prolonging the life expectancy.
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