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Is ALS a hereditary disease?


We have used the acronym because the full name was too long for the title. Its real name is Amyotrophic Lateral Sclerosis (ALS). It is also known as Lou Gehrig’s disease, named after the baseball player who was first diagnosed with it; or Charcot’s disease, named after the first doctor who described it, but both names were too long again. The most famous patient with this disease was probably physicist Stephen Hawking.

As we can see from the mentioned patients, it is a progressive neurodegenerative disease that affects the nerve cells in the brain. Specifically, the affected nerve cells are the motor neurons in the cerebral cortex (upper motor neurons), brainstem, and spinal cord (lower motor neurons).

The lack of motor neurons leads to muscle paralysis that progresses until it leads to death, without affecting cognitive or sensory functions. These people are prisoners in an increasingly rigid cage of flesh, unable to prevent it. There is no cure, and all treatments are focused on combating the symptoms.

Sexual and excretory functions are also unaffected, although it can cause sudden emotional disturbances. Despite the horror it is, it is not a painful disease, the patient does not feel pain in the affected areas nor from the worsening of the symptoms.

The final cause of death is usually due to respiratory failure, as there is atrophy of the muscles in the thoracic area that participate in the respiratory process. It is considered the most serious, and I’m afraid the most common, of the diseases affecting motor neurons.

It is a disease related to age, with the highest risk age between 60 and 70 years, with a predominance in men, with two out of every three affected being men. These aren’t too limiting characteristics in today’s population, which explains why there is on average one case for every 50,000 inhabitants.

¿La ELA es una enfermedad hereditaria?

A Pathology Shrouded in Mystery

This is a disease that, despite years of study, is surrounded by many questions. It is believed that, in general, the trigger is a defect in the ubiquitin 2 protein, which participates in the processes of degradation and elimination of other proteins.

During the process, cells undergo a series of damages, from oxidative stress to alterations in the cytoskeleton (and when most of your body is composed of axons and dendrites dependent on the cytoskeleton, this is a major issue).

Moreover, we have excitotoxic damage. This occurs due to an overactivation of glutamate receptors, causing a massive influx of calcium into the cell. The calcium, in turn, induces an enzymatic response and releases proteins from within the mitochondria, which ends up damaging cellular structures and ultimately leads to cell death or apoptosis. Excitotoxicity is also present in other nervous system diseases, such as Alzheimer’s or Parkinson’s disease.

There is neuroinflammation, by the way. In many neurodegenerative diseases, the immune system enters the brain to see what’s happening, causing inflammation and making everything worse.

Does this explain why the pathology is centered on motor neurons? No. It is another of the great mysteries. Many experts suspect that there must be a common characteristic among motor neurons, absent in other populations of nerve cells, which makes them vulnerable to the disease.

The More It Moves, the Less You Do

The diagnosis is clinical. Symptoms suggest ALS, and further tests are performed to rule out similar diseases. This means that it may take months from the initial suspicion of the disease to the final confirmation.

Among the first symptoms, we can highlight muscle spasms, cramps, stiffness, or weakness during the early stages of the disease. People around the patients may notice speech problems, fatigue in the limbs, and clumsiness.

As the disease progresses and intermediate stages are reached, the disease usually presents with worsening speech disorders, as well as dysphagia or difficulty swallowing, progressive loss of movement and weakness, to the point of requiring a wheelchair for mobility.

Its progression is not constant, varying between individuals and even between regions of the body. There may occasionally be stages of stability where it does not worsen for a period of time.

Since there is no cure, efforts are focused on symptoms and halting the progression as much as possible. Slowing down the deterioration.

Some of the drugs used, for example, inhibit the release of glutamate, which we mentioned earlier as causing excitotoxicity. Other medications used are antioxidants or stem cell treatments.

In addition to pharmacological treatments, specialists such as physical therapists or speech therapists collaborate to help patients maintain functional independence. For this reason, it is a disease with a multidisciplinary treatment approach.

Well, Is It Hereditary or Not?

Now we’re getting to that, patience. To talk about whether it’s a genetic disease or not, let’s look at its classification.

  • Sporadic ALS. The name indicates that its occurrence is random. There are no risk factors or ways to predict its appearance, and it is the most common form. This doesn’t exclude the involvement of genetic factors, only that they are unknown.
  • Familial ALS. These account for 5-10% of cases. It’s considered to occur due to an autosomal dominant variant, so it can be passed down within a family, and it typically occurs at an earlier average age than sporadic ALS.

In general, amyotrophic lateral sclerosis is not considered a hereditary disease. However, the presence of the disease in the family is taken into account as a risk factor and is included in medical histories. It’s a “this doesn’t necessarily mean anything but we’re noting it just in case”.

Four genes have been found to be altered in almost half of familial ALS cases, and up to 5% of sporadic cases: C9orf72, SOD1, FUS, and TARDBP.

It’s considered that genetics play a larger role in forms of ALS that occur early. In juvenile ALS, which occurs before the age of 25, it is common to find mutations in the FUS, ALS2, and SETX genes. Another genetic correlation found in the disease is between mutations of the FUS and SOD1 genes, and a negative progression of the pathology.

Of course, there are other risk factors and causes. From exposure to toxic substances, like some agricultural pesticides, to infections, from viral to fungal. It’s believed that in some patients the genetic conditions may start the disease asymptomatically at an early age, and environmental characteristics may later contribute to its severity until it becomes visible.

But it is an idiopathic disease, meaning it has an unknown cause and spontaneous origin. Put bluntly, we have no idea why it suddenly happens.

Idiopathic diseases are concerning, especially when they are complex. Don’t let fear paralyze you, try to predict this and other pathologies with the tellmeGen DNA Advanced kit.