Genetic disorder research

assignment: Amyotrophic lateral

sclerosis
Introduction
According to mayoclinic.org 2022, Amyotrophic lateral sclerosis (ALS) or motor neuron is a
neurological disorder characterised by the Atrophy or gradual deterioration of motor neurons
in the brain and spine, resulting in a loss of muscular function. The cause of ALS is not
known, and scientists do not yet know why ALS affects some people and not others.
However, a study done in 2016 suggests that both genetics and environment play a role in
motor neuron degeneration and the development of ALS (Kirby et al., 2016). According to
als.org It is estimated that 90 to 95 percent of ALS cases are sporadic, which means the
individual doesn't have a family history of the disease but. When an individual has a family
history of ALS, 5% to 10% of cases are familial ALS. This results from an inherited gene
mutation from a family member. A known ALS-associated genetic mutation is present in
around two-thirds of patients with familial ALS and 10% of those with sporadic ALS
(no family history). Additionally, ALS mutations can be passed down from parents who carry
the mutation. The majority of sporadic ALS cases have no known genetic cause. Then, ALS
could have been caused in part by risk factors related to lifestyle, the environment, or other
causes.

How is the disease inherited?

According to medlineplus.gov, 5 to 10 percent of cases of ALS are familial and are inherited.
Autosomal recessive and X-linked variants of familial ALS have been documented, while the
majority of cases are autosomal dominant. The pattern of inheritance varies based on the
gene concerned. Most cases are autosomal dominant, meaning that each cell only needs
one copy of the defective gene to develop the illness. Affected people frequently have one
parent who also has the disorder. Less commonly, ALS is passed down by an autosomal
recessive pattern of inheritance, meaning that both copies of the gene in every cell are
mutated. One copy of the defective gene is carried by each parent of a person with an
autosomal recessive disorder, although usually neither parent exhibits the disease's signs
and symptoms. Even though autosomal recessive ALS is brought on by a familial genetic
mutation, it is frequently misdiagnosed as sporadic ALS since the parents of a patient are
unaffected. Rarely does ALS have an X-linked dominant inheritance pattern. When the
genes linked to the disorder is found on the X chromosome, one of the two sex
chromosomes, the condition is said to be X-linked. The condition can only be brought on in
females (who have two X chromosomes) by if there is a mutation in one of the two copies of
the gene present in each cell. A mutation in the one copy of the gene in each cell in males
(who have only one X chromosome) causes the condition. 

Multiple gene mutations can lead to sporadic ALS and contribute to the onset of familial ALS.
According to molecularneurodegeneration.biomedcentral.com, In the United States and
Europe, 30 to 40% of familial ALS cases are caused by mutations in the C9orf72 gene.
SOD1 gene mutations contribute for 15 to 20% of familial ALS cases globally, whereas
TARDBP and FUS gene mutations each account for roughly 5% of cases. Each of the other
genes linked to familial ALS only accounts for a small fraction of cases. According to
estimates, 60 percent of those with familial ALS have a known genetic mutation. The
remaining individuals with the disorder has an unknown cause.
Autosomal dominant pattern:

Autosomal recessive pattern:

X-linked pattern:

What are the symptoms of the disease?

According to medlineplus.gov, Patients with sporadic ALS frequently have their first
symptoms in their late 50s or early 60s. An individual with familial ALS has its first signs and
symptoms in their 40s or early 50s and is inherited. Symptoms differ from person to person
depending on which neurons are affected (upper motor neurons) and (lower motor neurons).
Symptoms include, muscle tightness and cramps, both leg and arm muscles weakening and
loss of control, trouble speaking and swallowing, and cognitive and personality changes.

In the early stages of ALS signs can be difficulty doing basic everyday things such as picking
up items or walking. "Limb onset" ALS refers to the onset of symptoms in the arms or legs,
and "bulbar onset" ALS refers to the onset of symptoms in the speech or swallowing
muscles. Muscle atrophy and weakening expand to other body areas as the disorder
worsens. People may experience issues with their ability to move, swallow (dysphagia), talk
or form words (dysarthria), and breathe (dyspnea). Individuals gradually lose the ability to
stand or walk, get in or out of bed independently, or use their hands and arms, however the
order in which symptoms first appear and the speed at which the disease worsens might
vary from one person to another.

Within 3 to 5 years of their first initial diagnosis, most ALS patients pass away from
respiratory failure.
How is the disease managed?
There is no cure for ALS or a way to repair or stop the motor neurones atrophy. Treatments,
however, can reduce disease-related symptoms, avert unnecessary consequences, and
improve quality of life. The most effective way to deliver supportive treatment is through
multidisciplinary teams of specialists. These teams may develop a customised treatment
plan and offer specialised equipment meant to keep patients as agile, independent, and
comfortable as possible.

The medicine riluzole (Rilutek) is thought to lessen motor neurons damage by lowering

glutamate levels, which carry messages between nerve cells and motor neurons. Riluzole
extends survival in ALS patients by a few months, especially in the bulbar type of the illness,
according to clinical studies. Additionally, physical therapy and specialised equipment can
increase a person's independence.

Is there any hopeful current research being conducted to either

prevent, cure, or manage the disease?
The National Institute of Neurological Disorders and Stroke (NINDS) is conduct research on
the mechanisms underlying the death of motor neurone cells, the use of stem cells as
potential treatments, the comparison of familial and sporadic ALS cases to identify genes
involved in the disease's onset, the discovery of new biomarkers to assist patients in making
more accurate diagnoses, and the development of new drugs, stem-cell treatments,
antibodies, and gene therapies.
References
Miller, RG, Bouchard, JP, Duquette, P, Eisen, A, Gelinas, D, Harati, Y, Munsat, TL, Powe,
L, Rothstein, J, Salzman, P & Sufit, RL 1996, ‘Clinical trials of riluzole in patients with
ALS’, Neurology, vol. 47, no. Issue 4, Supplement 2, pp. 86S92S, viewed 2 August 2022, <
https://n.neurology.org/content/47/4_Suppl_2/86S.figures-only >.

‌What is ALS? 2022, The ALS Association, viewed 2 August 2022, <

https://www.als.org/understanding-als/what-is-als >.

Henderson, W 2017, What Research Is Being Done on ALS? – ALS News Today, ALS News
Today, viewed 2 August 2022, <
https://alsnewstoday.com/social-clips/research-done-als/#:~:text=Some%20of%20the
%20current%20research,the%20way%20the%20disease%20is >.

‌Amyotrophic Lateral Sclerosis (ALS) Fact Sheet | National Institute of Neurological

Disorders and Stroke 2021, Nih.gov, viewed 2 August 2022, <
https://www.ninds.nih.gov/amyotrophic-lateral-sclerosis-als-fact-sheet >.

Amyotrophic lateral sclerosis (ALS) - Diagnosis and treatment - Mayo Clinic 2022,

Mayoclinic.org, viewed 2 August 2022, <
https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/diagnosis-
treatment/drc-20354027 >.

Chen, S, Sayana, P, Zhang, X & Le, W 2013, ‘Genetics of amyotrophic lateral sclerosis: an
update’, Molecular Neurodegeneration, vol. 8, no. 1, viewed 2 August 2022, <
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-8-
28#Sec2 >.

Amyotrophic lateral sclerosis: MedlinePlus Genetics 2012, Medlineplus.gov, viewed 2

August 2022, < https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis/ >.