Amyotrophic lateral sclerosis type 2

Synonyms

Amyotrophic lateral sclerosis 2
Amyotrophic lateral sclerosis familial type 2
Amyotrophic lateral sclerosis juvenile
ALS2

Overview

Amyotrophic lateral sclerosis type 2 is an inherited form of Amyotrophic lateral sclerosis (ALS), which develops in a person's teens or twenties. ALS is characterized by progressive degeneration of motor neurons which results in muscle weakness and atrophy. An important gene associated with Amyotrophic Lateral Sclerosis Type 2 is ALS2 (amyotrophic lateral sclerosis 2 (juvenile)).

Symptoms

The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; slurred and nasal speech; breathing or swallowing muscles may be the first muscles affected. As the disease gets worse, more muscle groups develop problems. These general complaints then develop into more obvious weakness or atrophy that may cause a physician to suspect ALS.

Persons with ALS have a loss of muscle strength and coordination that eventually gets worse and makes it impossible to do routine tasks such as going up steps, getting out of a chair, or swallowing.

ALS does not affect the senses (sight, smell, taste, hearing, touch). It only rarely affects bladder or bowel function, eye movement, or a person's ability to think or reason.

Symptoms include:

  • Difficulty breathing
  • Difficulty swallowing
  • Choking easily
  • Drooling
  • Gagging
  • Head drop due to weakness of the neck muscles
  • Muscle cramps
  • Muscle contractions called fasciculations
  • Muscle weakness that slowly gets worse
  • Commonly involves one part of the body first, such as the arm or hand
  • Eventually leads to difficulty lifting, climbing stairs, and walking
  • Paralysis
  • Speech problems, such as a slow or abnormal speech pattern (slurring of words)
  • Voice changes, hoarseness
  • Weight loss

Causes

The exact cause of ALS is unknown, but about 5 to 10% of cases have a genetic component.

In patients with ALS type 2, mutations in ALS2 gene were found. The ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. This protein is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.

Alsin appears to have many functions, only a few of which are known. Alsin plays a role in cell division, the process by which cells mature to carry out specific functions (differentiation), and the self-destruction of cells (apoptosis). Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.

At least eight mutations in the ALS2 gene have been found to cause ALS. As a result of ALS2 gene mutations, alsin does not function correctly or does not function at all.

It is unclear how the loss of functional alsin protein causes ALS. A reduction in alsin function may interfere with essential pathways n the cell. Additionally, a lack of functional alsin may impair the movement of essential molecules into cells or alter the development of axons and dendrites. Researchers suggest that the long axons of motor neurons may be particularly sensitive to altered development. It is likely that a combination of these deficits in function eventually cause motor neurons to die, leading to the signs and symptoms of ALS.

ALS2 has an autosomal recessive type of inheritance. A mutation in a gene on one of the first 22 nonsex (autosomal) chromosomes can lead to an autosomal disorder. Genes come in pairs. An autosomal recessive disorder means both genes in a pair must be defective to cause disease. People with only one defective gene in the pair are considered carriers. However, they can pass the abnormal gene to their children.

Mutations in ALS2 gene also cause Juvenile primary lateral sclerosis.

Prevention

Genetics testing would be helpful if in the family history of ALS2.

Diagnosis

The diagnosis of ALS is primarily based on the symptoms and signs 

  • Weakness, often beginning in one area
  • Muscle tremors, spasms, twitching, or loss of muscle tissue
  • Twitching of the tongue (common)
  • Abnormal reflexes
  • Stiff or clumsy walk
  • Increased reflexes at the joints
  • Difficulty controlling crying or laughing (sometimes called emotional incontinence)
  • Loss of gag reflex

Tests that may be done include:

  • Blood tests to rule out other conditions
  • Breathing test to see if lung muscles are affected
  • Cervical spine CT or MRI to be sure there is no disease or injury to the neck, which can mimic ALS
  • Electromyography to see which nerves or muscles do not work properly
  • Genetic testing, if there is a family history of ALS
  • Head CT or MRI to rule out other conditions
  • Swallowing studies
  • Spinal tap (lumbar puncture)

Prognosis

Regardless of the part of the body first affected with the disease, muscle weakness and atrophy spread to other parts of the body and eventually of the respiratory. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure within 3 to 5 years from the onset of symptoms. About 25 percent of patients live more than 5 years after diagnosis.

Treatment

There is no known cure for ALS.

A medicine called Riluzole helps to slow down the symptoms and lets you live longer. The drug also may delay the need for a tracheostomy (breathing tube).

Treatments to control other symptoms include:

  • Baclofen or diazepam for spasticity that interferes with daily activities
  • Trihexyphenidyl or amitriptyline for people with problems swallowing their own saliva

Physical therapy, occupational therapy, and rehabilitation may help to prevent joint immobility and slow muscle weakness and atrophy.

Drugs are available to help individuals with pain, panic attacks, and depression

Patients with ALS tend to lose weight. The illness itself increases the need for food and calories. At the same time, problems with swallowing (resulting in chocking) make it hard to eat enough. Researchers have stated that ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake and encourage patients not to restrict their calorie intake. Patients may decide to use a gastrostomy (a surgical opening into the stomach for nutritional support through a tube).

Due to increasing problems with breathing, individuals with ALS may eventually consider forms of mechanical ventilation (respirators).

 

Resources

  • Genetic Home Reference
  • National Institute of Neurological Disorders and Stroke (US)
  • Medline Plus
  • NIH