Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of motor neurons, the nerve cells that control voluntary muscle movements. ALS is marked by symptoms that include muscle wasting (atrophy), and difficulty in breathing and going about everyday tasks, like dressing and eating.
ALS can be grouped into different forms. Most commonly, a grouping is based on the underlying cause of the disease, or whether it is sporadic or inherited. ALS can also be classified by the muscles it first affects, also known as the clinical onset of the disease.
Classification by underlying cause
Sporadic ALS is the most common form, accounting for around 90% to 95% of all cases. This form is diagnosed in patients who do not have a family history of the disease.
Genetic factors can slightly increase the risk of developing sporadic ALS, but they do not directly cause the disease itself.
Familial, or inherited, ALS runs in families and accounts for the remaining 5% to 10% of cases. It can be caused by one of several mutations that are passed from parents to their children. Familial ALS usually is inherited in an autosomal dominant manner, meaning that an affected person has a 50% chance of passing the disease-causing mutation to a child.
Several mutations have been identified and linked to familial ALS, and others may still be unknown.
The most common disease-causing mutation, associated with 25% to 40% of familial ALS cases, is in a gene called C9ORF72. Changes to this gene are also associated with frontotemporal dementia (FTD), a progressive condition that affects personality, speech, and behavior. People with a mutation in this gene may develop both diseases, referred to as ALS-FTD.
Other known genes associated with familial ALS include SOD1, TARDBP, FUS, and UBQLN2.
Classification by clinical onset
Around two-thirds of ALS patients have what is called the limb-onset form of the disease. Initial symptoms of this form include muscle weakness or wasting in the arms and legs, and involuntary muscle contractions resulting in twitches.
Early signs of this ALS form include loss of balance, trouble walking with constant tripping or stumbling, and difficulty performing tasks requiring fine dexterity. Patients with spinal ALS tend to progress to paralysis or death within three to five years.
In the bulbar-onset form of ALS, the muscles involved in speaking, swallowing, and breathing are generally the first to be affected. Initial symptoms include slurry speech and difficulty swallowing. However, muscle weakness can quickly progress to the arms and legs, making it difficult to distinguish between spinal and bulbar ALS.
Bulbar ALS is slightly more common in women, and in people over age 70. Although the progression of disease is variable, bulbar ALS tends to be faster progressing. Patients may be paralyzed and progress to respiratory failure within two to three years of onset.
Of note, since ALS tends to evolve in various areas of the body at the same time, it may not be immediately evident whether an individual has spinal or bulbar ALS at time of diagnosis.
Other forms of ALS
Another disease form is called ALS-parkinsonism-dementia complex 1 (ALS-PDC) or Guam disease, where patients experience symptoms of ALS, dementia, and Parkinson’s disease. It is especially common in people living in Guam and the Trust Territories of the Pacific. The exact cause of this form is not known, though recent research has implicated dietary toxins as a potential culprit.
Juvenile ALS is another extremely rare form of ALS that, as its name implies, affects children, adolescents, and young adults under age 25.
Last Updated: June 14, 2021
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