Recently, there have been a number of inquiries from patients about Amyotrophic Lateral Sclerosis (called as ALS) if it can be covered by the WES(Whole Exome Sequencing) test.

As per request, it will be an excellent time to understand what ALS is and its details.

What is amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis affects nerve cells in the brain and the spinal cord

Amyotrophic lateral sclerosis (ALS) was once commonly known as Lou Gehrig’s disease. It is a progressive neurodegenerative rare disease that affects nerve cells in the brain and the spinal cord. This affects the control of muscles which leads to weakness and wasting of muscle.1

Types of amyotrophic lateral sclerosis

Familial amyotrophic lateral sclerosis(FALS) takes 5 to 10 percent of All ALS, while sporadic amyotrophic lateral sclerosis(SALS) takes 90 to 95 percent of all ALS

There are two types of ALS; FALS and SALS.

FALS (Familial amyotrophic lateral sclerosis) arises in families with a history of ALS, and this case is about 5 to 10 percent of ALS. Several genes associated with ALS have been identified or at least mapped to a specific region of a chromosome.

The other 90 to 95 percent of ALS is SALS (Sporadic amyotrophic lateral sclerosis), which occurs without a family history. The genetic variations appear to influence one's susceptibility to SALS, even if they are not necessarily causing the disease themselves. Moreover, some of the same genes identified to cause FALS have been found in patients with SALS.2

Inheritance pattern of amyotrophic lateral sclerosis

A family tree showing that FALS follows autosomal dominant inheritance pattern. SALS usually occurs from de novo mutation of the patient

FALS is most often autosomal dominant. It refers that a parent who has an ALS- causing genetic variant has a 50% chance of passing the same thing to his or her children regardless of gender.3

Some cases of SALS, the family history may not be known yet. Meaning, parents may have passed away before showing signs of the disease.

Onset and symptoms of amyotrophic lateral sclerosis

Six early symptoms of ALS: Muscle cramps, Tight and stiff muscles, Muscle weakness, Slurred and nasal speech, Difficulty chewing or swallowing, Paralysis

Most people who develop ALS are between 40 and 70, although the disease can occur at a younger age. People with FALS often start showing symptoms at earlier ages than in SALS.4

The onset of ALS can be so subtle that the symptoms are overlooked, but gradually these symptoms develop into more obvious weakness or atrophy.

The followings are early symptoms;

  • Muscle twitches in the arm, leg, shoulder, or tongue
  • Muscle cramps
  • Tight and stiff muscles (spasticity)
  • Muscle weakness affecting an arm, a leg, the neck, or diaphragm
  • Slurred and nasal speech
  • Difficulty chewing or swallowing
  • Paralysis4

How is amyotrophic lateral sclerosis diagnosed?

There are more than 12 different gene variants that have been linked to ALS. One change is to a gene that makes a protein called SOD1. This protein may be toxic to motor neurons. Other gene variants in ALS can also damage motor neurons.2

Besides the known genetic variants of ALS, the latest genetic causes of ALS are also being discovered just in 2021.5 These are SPLTC1 and TP73 genes.6

More than 5,000 people are diagnosed with ALS every year.

To diagnose many ALS-causing gene mutations, genetic testing is available. WES can cover genes related to ALS and newly discovered other ALS causing genes with its fast updates from Online Mendelian Inheritance in Man (OMIM), where every disease-causing genetic mutation is listed. By doing a WES test with biological parents, it is possible to find out if it is FALS or SALS as well at once. It definitely saves time and prevents a diagnostic odyssey.

Physicians who see more than 30 new patients with ALS per year were significantly more likely to offer diagnostic genetic testing to patients.7

Treatment for amyotrophic lateral sclerosis, Rilutek

Many rare genetic diseases do not have a treatment yet. Fortunately, there is a treatment for patients diagnosed with ALS, and it is a medication called ‘Rilutek’, containing the active substance riluzole.

Rilutek is indicated to extend life or mechanical ventilation for patients with amyotrophic lateral sclerosis (ALS). Clinical trials have demonstrated that Rilutek extends survival for patients with ALS.8

It is vital to save time to diagnose ALS because Rilutek has not been shown to be effective in the late stages of ALS.

If any of your patients are suspected of having ALS, please consider taking a genetic test promptly to help you diagnose them. A genetic counselor can help interpret test results and discuss their implications for the person with ALS and his or her family.9 The most common use of genetic testing for ALS is to provide risk information and subsequent counseling for unaffected at-risk family members. As there is medication available and effective in early stages of ALS, it is crucial to diagnose them as soon as possible.

References

  1. WebMD. Understanding ALS basics
  2. Muscular Dystrophy Association. Amyotrophic lateral sclerosis
  3. The ALS Association. What is Als?
  4. Johns Hopkins medicine. ALS, Amyotrophic Lateral Sclerosis
  5. National Institutes of Health. Scientists discover a new genetic form of ALS in children
  6. US news. New genetic insights into cause of ALS
  7. Vajda A, McLaughlin RL, Heverin M, et al. Genetic testing in ALS: A survey of current practices. Neurology. ;88(10):991-999. (2017).
  8. European Medicines Agency. Rilutek
  9. Hospital for Special Surgery. How is ALS diagnosed and treated?

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