Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive disease that causes the death of motor neurons, leading to muscle weakness, atrophy, and eventually the loss of the ability to control movement.
Overview
ALS affects motor neurons, the specialized nerve cells that control muscle movement. As these cells die over time, individuals experience muscle weakness, loss of muscle mass, and an inability to control movement. Most cases are sporadic, occurring in people with no family history of the disorder. A small percentage (5 to 10 percent) is familial, meaning it is inherited.
Symptoms
- Muscle twitching, cramping, stiffness, or weakness
- Slurred speech (dysarthria)
- Difficulty chewing or swallowing (dysphagia)
- Malnutrition due to swallowing difficulties
- Progressive loss of muscle strength and ability to walk
- Respiratory muscle weakness
Some individuals may also develop frontotemporal dementia (FTD), which affects personality, behavior, and communication. A rare form, ALS-parkinsonism-dementia complex (ALS-PDC), includes movement abnormalities such as slow movements (bradykinesia), stiffness, and tremors.
Causes
The cause of sporadic ALS is largely unknown but likely involves a combination of genetic and environmental factors. Familial ALS is caused by mutations in several genes, most notably C9orf72, SOD1, TARDBP, and FUS. These mutations are thought to disrupt the function of motor neurons, potentially through the buildup of protein clumps (aggregates) or by impairing the transmission of nerve impulses to muscles.
Inheritance
While 90 to 95 percent of cases are sporadic, familial ALS can be inherited in several ways:
- Autosomal dominant: One copy of the altered gene is sufficient to cause the disorder.
- Autosomal recessive: Both copies of the gene must have mutations to cause the disorder.
- X-linked: The mutation occurs on the X chromosome; this is very rare.