Amyotrophic lateral sclerosis
Other Names for this Disease
- Amyotrophic lateral sclerosis type 1
- Charcot disease
- Lou Gehrig disease
What causes amyotrophic lateral sclerosis?
Is amyotrophic lateral sclerosis (ALS) inherited?
Is genetic testing available for amyotrophic lateral sclerosis?
How might amyotrophic lateral sclerosis (ALS) be treated?
The remaining 5-10% of cases are genetic (familial), often occurring in individuals with a family history of the condition. Mutations in any of several genes, including the C9orf72, SOD1, TARDBP, FUS, ANG, ALS2, SETX, and VAPB genes, can cause familial ALS and may contribute to the development of sporadic ALS. About 60% of individuals with familial ALS have an identifiable genetic mutation; the genetic cause in the remaining cases is unknown. The genes associated with ALS appear to play a role in how neurons function or are involved in regulating the production of various proteins.
Over the years, various types of environmental exposures have been proposed as possible contributors to the cause of ALS, including mercury, manganese, products used in farming (fertilizers, insecticides, herbicides), and physical and dietary factors. Exposures have been suggested as a possible explanation for the increased incidence of ALS in Gulf War veterans. Further investigation is ongoing.
Most familial cases are inherited in an autosomal dominant manner. This means that only one altered (mutated) copy of the disease-causing gene in each cell is sufficient to cause the condition. In most of these cases, an affected individual has one parent with the condition. When an individual with an autosomal dominant form of ALS has children, each child has a 50% (1 in 2) risk to inherited the mutated copy of the gene and be affected.
Less frequently, ALS is inherited in an autosomal recessive manner. In autosomal recessive inheritance, both copies of the disease-causing gene (typically one copy inherited from each parent) must have a mutation for the individual to be affected. The parents of an individual with an autosomal recessive condition, who presumably each carry one mutated copy of the gene, are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for the same condition are having children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each parent, and a 25% risk to not have the condition and not be a carrier. Autosomal recessive forms of ALS may be mistaken for non-inherited (sporadic) forms due to having a negative family history of the condition.
In rare cases, ALS is inherited in an X-linked dominant manner. This occurs when the disease-causing gene is located on the X chromosome (a sex chromosome). Although females have 2 X chromosomes, having a mutation in one X chromosome is still sufficient to cause the condition. Males who have a mutation (and only one X chromosome) will have the condition. Usually, males with an X-linked dominant form of ALS experience more severe symptoms than females with the same form.
Some individuals who do inherit a mutation known to cause ALS never develop signs and symptoms of ALS, although the reason for this is unclear. This phenomenon is referred to as reduced penetrance.
You can find laboratories offering clinical and research genetic testing for ALS on a Web site called GeneTests. To see GeneTests' list of the types of ALS for which genetic testing is available, click here. Click on "Testing" next to each type of ALS of interest to see a list of the laboratories that offer clinical testing. Click on "Research" next to each type of ALS of interest to see a list of the laboratories that offer research testing.
Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families. Therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.
The Food and Drug Administration (FDA) has approved the first drug treatment for the disease—riluzole (Rilutek). Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole prolongs survival by several months, mainly in those with difficulty swallowing. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects.
Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients (palliative care). This supportive care is typically provided by multidisciplinary teams of health care professionals such as physicians; pharmacists; physical, occupational, and speech therapists; nutritionists; social workers; and home care and hospice nurses. Working with patients and caregivers, these teams can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.
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 therapy and special equipment can enhance patients' independence and safety throughout the course of ALS. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve energy and remain mobile. ALS patients who have difficulty speaking may benefit from working with a speech therapist. Patients and caregivers can learn from speech therapists and nutritionists 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, and 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.
- Donkervoort S, Siddique T. Amyotrophic Lateral Sclerosis. GeneReviews . 2009; http://www.ncbi.nlm.nih.gov/books/NBK1450/. Accessed 4/12/2011.
- Amyotrophic lateral sclerosis. Genetics Home Reference. August 2012; http://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis. Accessed 1/7/2013.
- Nigel Leigh and Lokesh Wijesekera. Amyotrophic lateral sclerosis. Orphanet. May 2011; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=803. Accessed 1/7/2012.
- Lisa Kinsley and Teepu Siddique. Amyotrophic Lateral Sclerosis Overview. GeneReviews. May 31, 2012; http://www.ncbi.nlm.nih.gov/books/NBK1450/. Accessed 1/11/2013.
- Amyotrophic Lateral Sclerosis Fact Sheet. National Institute of Neurological Disorders and Stroke. October 21, 2010; http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_amyotrophiclateralsclerosis.htm#163974842. Accessed 11/4/2010.
- Lisa Dellefave, MS, CGC . Amyotrophic Lateral Sclerosis Overview. Genetic Reviews. http://www.genetests.org/query?dz=als-overview. Accessed 10/9/2007.