Lou Gehrig's Disease (ALS)

Sam Janis

Clinical Defenition

A nervous system (neurological) disease that causes muscle weakness and impacts physical function.

Common Names

  • Amyotrophic lateral sclerosis

  • Lou Gehrig’s disease

  • Charcot’s disease (Parts of Europe)

  • Maladie de Charcot (France)

  • Motor Neuron Disease (England)
A.L.S. - Lou Gehrig's disease

Statistical Information

Every day, an average of 15 people are newly diagnosed with ALS — more than 5,600 people per year. As many as 30,000 Americans may currently be affected by ALS. Annually, ALS is responsible for two deaths per 100,000 people. The average life expectancy of a person with ALS is two to five years from time of diagnosis. With recent advances in research and improved medical care, many patients are living longer, more productive lives. Half of all those affected live at least three years or more after diagnosis. About 20 percent live five years or more, and up to ten percent will survive more than ten years. 60% of people in the ALS data base are men.


http://www.alsa.org/about-als/facts-you-should-know.html

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Proteins that Cause ALS

  • TDP-43 - The TDP-43 protein attaches (binds) to DNA and regulates an activity called transcription, which is the first step in the production of proteins from genes. This protein can also bind to RNA, a chemical cousin of DNA, to ensure the RNA's stability. The TDP-43 protein is involved in processing molecules called messenger RNA (mRNA), which serve as the genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the TDP-43 protein controls the production of different versions of certain proteins. This process is known as alternative splicing. The TDP-43 protein can influence various functions of a cell by regulating protein production.
  • SOD1- converts reactive oxygen to harmless water. A copper ion held within the enzyme carries out this chemical change. A zinc atom is also important to the enzyme’s function. This enzyme serves to keep cells safe from metabolic waste that can do damage if not rendered harmless.
  • C9ORF72- The C9ORF72 gene provides instructions for making a protein that is found in various tissues. The protein is abundant in nerve cells in the outer layers of the brain and in specialized neurons in the brain and spinal cord that control movement (motor neurons).

Mutations that Cause ALS

  • SOD1- Early studies of mutant SOD1 provided evidence that disease is not caused by loss of this enzyme’s activity. It is now widely accepted that the mutations must cause SOD1 to gain a toxic property. Several reasons for the toxicity are proposed, but none are proven.About half of all Americans with ALS caused by SOD1 gene mutations have a particular mutation that replaces the amino acid alanine with the amino acid valine at position 5 in the enzyme. The most popular mutation is an Ala5Val mutation.
  • C9ORF72- The C9ORF72 gene may cause ALS due to accumulations of RNA that occur when the gene is mutated. This is not fully proven. These mutations affect the GGGGCC segment of the gene. When this series of nucleotides is repeated too many times, it can cause ALS. This type of mutation is called a hexanucleotide repeat expansion.
  • TDP-43- mutations may impair the normal processing of RNA from a wide variety of genes, leading to ALS. Most mutations change single protein building blocks (amino acids) in the TDP-43 protein. The majority of these changes affect the region of the protein involved in mRNA processing, likely disrupting the production of other proteins. This is a point mutation.
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Patterns of Inheritance

For most ALS genes, only one mutated copy is needed to cause disease. For other genes, both copies must be mutated to cause disease.


Initial Symptoms

Initial symptoms include: fasciculations, cramps, tight and stiff muscles (spasticity), muscle weakness affecting an arm or a leg, slurred and nasal speech, or difficulty chewing or swallowing. ALS starts in one area and gradually moves to other parts over time.


Later Symptoms

Patients have increasing problems with moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign (the large toe extends upward as the sole of the foot is stimulated in a certain way) also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, Muscle Cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations).

How to diagnose ALS

  • Blood tests: a doctor may use blood tests to check for the enzyme creatine kinase, which leaks out of damaged muscle
  • Cerebrospinal fluid examination
  • Electromyogram: An EMG can indicate if motor neurons aren’t working, a sign showing ALS
  • Genetic Testing: Looking for familial signs of ALS
  • Magnetic resonance imaging (MRI)
  • Muscle Biopsy

Treatments for ALS

ALS is a terminal disease, all treatments are ways to improve way of life and to make you more comfortable. Riluzole (Rilutek) is the only approved medication by the Food and Drug administration for ALS.This drug reduces the progression of the disease in certain people. Breathing care is used for when the disease progresses to the point where breathing becomes hard. Physical, Occupational, Speech, etc. therapy is used when the weakening of muscles happens. Nutritional support is used when food becomes hard to eat, and help is needed to find the right nutrition. Psychological and Social support is used for when you need help with tasks such as paying for equipment, doing taxes, insurance, and for the mental stability of friends and family.

Ethical Implications of Diagnosis and Treatment

Each person diagnosed with ALS reaches the point where they realizes that they have ALS.This realization forces the patient to decide whether he or she wants to continue life via gastrostomy tube insertion, mechanical ventilation or both or to forego these treatments in favor of hospice care. The clinician should realize that the determination of decisions may be compromised, so it is important to talk about life threatening symptoms,capacity for decision making, possible end of life scenarios, symptoms.

Resources

"Amyotrophic Lateral Sclerosis." (ALS). N.p., n.d. Web. 20 Mar. 2016. <http://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/basics/definition/con-20024397>.


"Amyotrophic Lateral Sclerosis." Wikipedia. Wikimedia Foundation, n.d. Web. 20 Mar. 2016. <https://en.wikipedia.org/wiki/Amyotrophic_lateral_sclerosis>.


"Quick Facts About ALS & The ALS Association." ALSA.org. N.p., n.d. Web. 20 Mar. 2016. <http://www.alsa.org/news/media/quick-facts.html?referrer=https%3A%2F%2Fwww.google.com%2F>.


Miller, Greg. "Same Mutation Causes Lou Gehrig's Disease and Dementia."Same Mutation Causes Lou Gehrig's Disease and Dementia. N.p., 21 Sept. 2011. Web. 17 Mar. 2016. <http://www.sciencemag.org/news/2011/09/same-mutation-causes-lou-gehrigs-disease-and-dementia>.


"Genetics of ALS." ALSA.org. N.p., n.d. Web. 20 Mar. 2016. <http://www.alsa.org/research/about-als-research/genetics-of-als.html?referrer=https%3A%2F%2Fwww.google.com%2F>.


"Amyotrophic Lateral Sclerosis (ALS) Symptoms, Causes, Treatment - Amyotrophic Lateral Sclerosis Facts* - MedicineNet." MedicineNet. N.p., n.d. Web. 20 Mar. 2016. <http://www.medicinenet.com/amyotrophic_lateral_sclerosis/page2.htm


"TARDBP Gene." Genetics Home Reference. N.p., n.d. Web. 20 Mar. 2016. <https://ghr.nlm.nih.gov/gene/TARDBP>.


"Studies Confirm Region of Chromosome 9 Linked to Risk for Amyotrophic Lateral Sclerosis." Studies Confirm Region of Chromosome 9 Linked to Risk for Amyotrophic Lateral Sclerosis. N.p., n.d. Web. 20 Mar. 2016. <http://phys.org/news/2010-08-region-chromosome-linked-amyotrophic-lateral.html>.


"C9orf72 Gene." Genetics Home Reference. N.p., n.d. Web. 20 Mar. 2016. <https://ghr.nlm.nih.gov/gene/C9orf72>.


"TARDBP Gene." Genetics Home Reference. N.p., n.d. Web. 20 Mar. 2016. <https://ghr.nlm.nih.gov/gene/TARDBP>.


"SOD1 Gene." Genetics Home Reference. N.p., n.d. Web. 20 Mar. 2016. <https://ghr.nlm.nih.gov/gene/SOD1>.


"Amyotrophic Lateral Sclerosis." (ALS) Diagnosis at Mayo Clinic. N.p., n.d. Web. 20 Mar. 2016. <http://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/care-at-mayo-clinic/tests-diagnosis/con-20024397>.


"Amyotrophic Lateral Sclerosis." (ALS) Treatments and Drugs. N.p., n.d. Web. 20 Mar. 2016. <http://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/basics/treatment/con-20024397>.


"Famous People with Amyotrophic Lateral Sclerosis Lou Gehrigs Disease."Disabled World. N.p., n.d. Web. 20 Mar. 2016. <http://www.disabled-world.com/artman/publish/famous-als.shtml>.


"Facts You Should Know." ALSA.org. N.p., n.d. Web. 20 Mar. 2016. <http://www.alsa.org/about-als/facts-you-should-know.html>.


"Neurowiki 2014." Genetics of ALS -. N.p., n.d. Web. 20 Mar. 2016. <http://neurowiki2014.wikidot.com/individual:genetics-of-als>.