Amyotrophic Lateral Sclerosis 1 (ALS1)

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MedlinePlus Genetics: ⁴² Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.There are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.The first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.Approximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.A rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms.

MalaCards based summary: Amyotrophic Lateral Sclerosis 1, also known as amyotrophic lateral sclerosis, is related to frontotemporal dementia and/or amyotrophic lateral sclerosis 1 and frontotemporal dementia, and has symptoms including ataxia, tremor and myoclonus. An important gene associated with Amyotrophic Lateral Sclerosis 1 is SOD1 (Superoxide Dismutase 1), and among its related pathways/superpathways are Neuroscience and Physico-chemical features and toxicity-associated pathways. The drugs Riluzole and Mexiletine have been mentioned in the context of this disorder. Affiliated tissues include Bone and Limb, and related phenotypes are amyotrophic lateral sclerosis and generalized muscle weakness

GARD: ¹⁹ Amyotrophic lateral sclerosis (ALS), also referred to as "Lou Gehrig's disease," is a motor neuron disease which leads to problems with muscle control and movement. There are various types of ALS that are distinguished by symptoms and, in some cases, genetic cause. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. As the disease progresses, people may become weaker and are eventually wheelchair-dependent. 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 (pathogenic 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 genetic changes (pathogenic variants) 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. Diagnosis of ALS is based on symptoms and a variety of tests to rule out other possible medical diseases that can cause similar symptoms.

OMIM®: ⁵⁷ Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. Rowland and Shneider (2001) and Kunst (2004) provided extensive reviews of ALS. Some forms of ALS occur with frontotemporal dementia (FTD); see 105500. Ranganathan et al. (2020) provided a detailed review of the genes involved in different forms of ALS with FTD, noting that common disease pathways involve disturbances in RNA processing, autophagy, the ubiquitin proteasome system, the unfolded protein response, and intracellular trafficking. The current understanding of ALS and FTD is that some forms of these disorders represent a spectrum of disease with converging mechanisms of neurodegeneration. Familial ALS is distinct from a form of ALS with dementia reported in cases on Guam (105500) (Espinosa et al., 1962; Husquinet and Franck, 1980), in which the histology is different and dementia and parkinsonism complicate the clinical picture. (105400) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot ⁷³ Amyotrophic lateral sclerosis 1: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.

Amyotrophic lateral sclerosis: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.

NINDS: ⁵² Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal disease that affects the nerve cells (neurons) in that brain and spinal cord that  control voluntary muscle movement.  Our voluntary muscles produce movements like walking, breathing, chewing, and talking.  Nerve cells called motor neurons--that connect from the brain and spinal cord to the rest of the body--begin to degenerate and die, and stop sending messages to muscles. The muscles gradually weaken, waste away, and twitch, and the brain can't start and control voluntary movement.  Symptoms are usually first noticed in the arms and hands, legs, or swallowing muscles.  People with ALS lose their strength and become unable to move their arms and legs, and to hold the body upright.  Some individuals eventually can't breathe on their own.  Although ALS doesn't usually impair a person's mind or personality, several recent studies suggest that some people with ALS may develop cognitive problems involving word fluency, decision-making, and memory.  Most cases of ALS happen with no known cause, while a small percentage of cases are inherited.

MedlinePlus: ⁴¹ Amyotrophic lateral sclerosis (ALS) is a nervous system disease that attacks nerve cells called neurons in your brain and spinal cord. These neurons transmit messages from your brain and spinal cord to your voluntary muscles - the ones you can control, like in your arms and legs. At first, this causes mild muscle problems. Some people notice: Trouble walking or running Trouble writing Speech problems Eventually, you lose your strength and cannot move. When muscles in your chest fail, you cannot breathe. A breathing machine can help, but most people with ALS die from respiratory failure. The disease usually strikes between age 40 and 60. More men than women get it. No one knows what causes ALS. It can run in families, but usually it strikes at random. There is no cure. Medicines can relieve symptoms and, sometimes, prolong survival. NIH: National Institute of Neurological Disorders and Stroke

CDC: ² Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal disease, attacking neurons that control voluntary movement. These neurons die over time. The result is the gradual loss of muscle movement, speech, swallowing, and eventually, breathing. Unfortunately, people with ALS usually have a shortened lifespan and may die within a few years of diagnosis. ALS is most common in whites, males, and people over the age of 60. There are between 24,000 and 31,000 people living with ALS in United States as of 2017.

Disease Ontology ¹¹ Amyotrophic lateral sclerosis type 1: The most common type of familial ALS that has material basis in mutation in the SOD1 gene on chromosome 21.

Amyotrophic lateral sclerosis: A motor neuron disease that is characterized by muscle spasticity, rapidly progressive weakness due to muscle atrophy, difficulty in speaking, swallowing, and breathing.

Orphanet: ⁵⁸ A neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.

Wikipedia ⁷⁵ Amyotrophic lateral sclerosis: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease,... more...

Charcot disease: Charcot-Marie-Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous... more...

Clinical features from OMIM®:

Search NIH Clinical Center for Amyotrophic Lateral Sclerosis 1