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Disease Profile

Amyotrophic lateral sclerosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adult

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ICD-10

G12.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

ALS; Lou Gehrig disease; Amyotrophic lateral sclerosis type 1;

Categories

Nervous System Diseases

Summary

Amyotrophic lateral sclerosis (ALS), also referred to as "Lou Gehrig's disease," is a progressive motor neuron disease which leads to problems with muscle control and movement.[1][2] There are various types of ALS that are distinguished by symptoms and, in some cases, genetic cause.[2] Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. As the disease progresses, people become weaker and are eventually wheelchair-dependent. Death often results from respiratory failure within 2 to 10 years after the symptoms begin.[2][3]

Most people with ALS have a sporadic (not inherited) form of ALS. It is believed that these cases are caused by an interaction between genetic and environmental factors. This means that a person may have inherited genetic changes (variants) that increase their risk to develop ALS, but the person will only develop ALS if exposed to certain environmental triggers. About 10% of the people with ALS have at least one relative with the disease and are said to have have a familial (inherited) form of the disease (FALS). Familial ALS may be caused by changes (pathogenic variants, also known as mutations) in any one of several genes and the pattern of inheritance varies depending on the gene involved. The distinction between sporadic and familial cases is not always clear.[2][3] The average age at which symptoms begin is 56 years old in the sporadic cases and 46 years old in the familial cases.[1] 

Diagnosis of ALS is based on symptoms and a variety of tests to rule out other possible medical diseases that can cause similar symptoms.[1][4] The goal of treatment is to improve the quality of life for people with ALS, by assisting with breathing, nutrition, mobility, and communication.[3][5] Medications specifically approved for the treatment of ALS in the United States include riluzole and edaravone.[6][7]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Amyotrophic lateral sclerosis
0007354
80%-99% of people have these symptoms
Generalized muscle weakness
0003324
Neurodegeneration
Ongoing loss of nerve cells
0002180
30%-79% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Depressivity
Depression
0000716
Dyspnea
Trouble breathing
0002094
Emotional lability
Emotional instability
0000712
Fatigable weakness of respiratory muscles
0030196
Fatigable weakness of swallowing muscles
0030195
Fatigue
Tired
Tiredness

[ more ]

0012378
Muscle spasm
0003394
Pain
0012531
Paralysis
Inability to move
0003470
Respiratory failure
0002878
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Xerostomia
Dry mouth
Dry mouth syndrome
Reduced salivation

[ more ]

0000217
5%-29% of people have these symptoms
Agitation
0000713
Laryngospasm
0025425
Nausea and vomiting
0002017
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Degeneration of anterior horn cells
0002398
Degeneration of the lateral corticospinal tracts
0002314
Fasciculations
Muscle twitch
0002380
Hyperreflexia
Increased reflexes
0001347
Muscle weakness
Muscular weakness
0001324
Pseudobulbar paralysis
0007024
Sleep apnea
Pauses in breathing while sleeping
0010535

Diagnosis

Diagnosis of amyotrophic lateral sclerosis (ALS) may be suspected due to symptoms and the history of the way the symptoms progressed. ALS is usually strongly considered if the symptoms suggest both upper and lower motor neurons are affected. Basically, upper motor neurons (UPN) are found in the brain, whereas lower motor neurons are found in the spinal cord (LMN). UMN problems that can be found in a physical exam include tight and stiff muscles (spasticity), quicker than normal reflexes, and the Babinski reflex, which is when stroking the bottom of the foot causes the big toe to move upward and is not normally present after the age of 2 years. LMN problems that can be found in a physical exam include loss of muscle mass (muscle atrophy), muscle weakness, and muscle twitching (fasciculations). These signs can occur in any muscle group, including the arms, legs, chest, abdomen, and back, as well as the muscles involved in breathing, speaking, and swallowing. Even if symptoms of UMN and LMN problems are found, further testing must rule out other possible causes.[1][4]

Tests to rule out other possible diseases and medical causes include electromyography (EMG), nerve conduction study (NCS), magnetic resonance imaging (MRI) of brain and spinal cord, and urine and blood tests. After ALS is diagnosed, genetic testing may also be considered depending on family history, age the symptoms began, and the person's wishes.[1][4]

Treatment

Riluzole and endaravone are the two therapies approved by the United States Food and Drug Administration (FDA) specifically for the treatment of amyotrophic lateral scelerosis (ALS). Riluzole has been available in tablet form for over twenty years. It is believed to reduce damage to motor neurons. Riluzole may increase survival by several months and also extend the time before mechanical breathing support (ventilation) is needed. Riluzole does not reverse damage already done to motor neurons. The tablet form is available in generic versions and has been approved by the drug regulating agencies of most countries.[6][7] As of 2018, a liquid form, Tiglutik, has been approved by the FDA, which allows those who have a hard time swallowing a tablet to continue treatment.[8] 

Edaravone (Radicava) has been available in the United States since 2017. It is an antioxidant and may slow the decline of physical function in some people with ALS. Physical function is measured by ALS Functional Rating Scale-Revised (ALSDRS-R). This scale measures problems with speech, swallowing, and breathing, as well as daily functioning such as walking, holding items like a pen or fork, dressing, and general care of oneself, like bathing. Edaravone does not improve function that has already been lost. The clinical trials took place in Japan and were six months long. As of 2018, long term effects of treatment with edaravone on physical function, survival, and quality of life are not known. It can be used along with riluzole. Edaravone is delivered by IV infusion on usually a two week on, two week off cycle. The IV infusion takes about one hour and is initially given in a hospital or clinic setting, but many have been able to transition to having the IV infusions at home.[6][7] Edaravone is also approved by regulating agencies in Japan and South Korea, and is waiting for approval in Canada, Switzerland, and the European Union as of 2018.

Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This type of care is known as palliative care, supportive care that is typically provided by multidisciplinary teams of health care professionals such as physicians, pharmacists, physical therapists, occupational therapists, speech therapists, nutritionists, social workers, and home care and hospice nurses. These teams along with the patients and caregivers can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.[4]

  • Physicians: Can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, and constipation.
  • Pharmacists: Can give advice on the proper use of medications and monitor a patient's prescriptions to avoid risks of drug interactions.
  • Physical therapist: Can provide physical therapy and recommend special equipment to help the patient be independent and safe during the course of their ALS.
  • Occupational therapists: Can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve energy and remain mobile.
  • Speech therapists: Can provide speech therapy to those people with ALS who have difficulty speaking.
  • Nutritionists: Can help teach people with ALS and their caregivers how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. 
  • Social workers and home care and hospice nurses: Help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease.
  • Respiratory therapists: Can help caregivers with tasks such as operating and maintaining respirators.
  • Home care nurses: Are available not only to provide medical care but also to teach caregivers about giving tube feedings and moving patients to avoid painful skin problems and contractures.
  • Home hospice nurses: Work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home.

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Amyotrophic lateral sclerosis. This website is maintained by the National Library of Medicine.
      • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Amyotrophic lateral sclerosis in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Amyotrophic lateral sclerosis. Click on the link to view a sample search on this topic.

          References

          1. Kinsley L, Siddique T. Amyotrophic Lateral Sclerosis Overview. GeneReviews. February 12, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1450/.
          2. Amyotrophic lateral sclerosis. Genetics Home Reference. August 2012; https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis.
          3. ALS: Amyotrophic Lateral Sclerosis. Muscular Dystrophy Association (MDA). 2017; https://www.mda.org/disease/amyotrophic-lateral-sclerosis.
          4. Amyotrophic Lateral Sclerosis Fact Sheet: How is ALS treated?. National Institute of Neurological Disorders and Stroke. September 8, 2018; https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Sclerosis-ALS-Fact-Sheet.
          5. Nigel Leigh and Lokesh Wijesekera. Amyotrophic lateral sclerosis. Orphanet. May 2011; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=803.
          6. Takei K, Tsuda K, Takahashi F, Hirai M, Palumbo J. An assessment of treatment guidelines, clinical practices, demographics, and progression of disease among patients with amyotrophic lateral sclerosis in Japan, the United States, and Europe. Amyotroph Lateral Scler Frontotemporal Degener. October 2017; 18(sup1):88-97. https://www.ncbi.nlm.nih.gov/pubmed/28872912.
          7. Schultz J. Disease-modifying treatment of amyotrophic lateral sclerosis. Am J Manag Care. August 2018; 24(15 Suppl):S327-S335. https://www.ncbi.nlm.nih.gov/pubmed/30207671.
          8. Brooks M. FDA Clears Liquid Riluzole (Tiglutik) for ALS. MedScape Reference. September 6, 2018; https://www.medscape.com/viewarticle/901644.

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