Amyotrophic Lateral Sclerosis

Understanding the condition

From: MedlinePlus, National Library of Medicine

Amyotrophic lateral sclerosis (ALS) is a nervous system disease that attacks nerve cells called neurons in your brain and spinal cord. These neurons transmit messages from your brain and spinal cord to your voluntary muscles - the ones you can control, like in your arms and legs. At first, this causes mild muscle problems. Some people notice:

• Trouble walking or running
• Trouble writing
• Speech problems

Eventually, you lose your strength and cannot move. When muscles in your chest fail, you cannot breathe. A breathing machine can help, but most people with ALS die from respiratory failure.

The disease usually strikes between age 40 and 60. More men than women get it. No one knows what causes ALS. It can run in families, but usually it strikes at random. There is no cure. Medicines can relieve symptoms and, sometimes, prolong survival.

Genetic causes described in the linked summary

From: MedlinePlus Genetics

Mutations in several genes can cause familial ALS and contribute to the development of sporadic ALS. Mutations in the C9orf72 gene account for 30 to 40 percent of familial ALS in the United States and Europe. Worldwide, SOD1 gene mutations cause 15 to 20 percent of familial ALS, and TARDBP and FUS gene mutations each account for about 5 percent of cases. The other genes that have been associated with familial ALS each account for a small proportion of cases. It is estimated that 60 percent of individuals with familial ALS have an identified genetic mutation. The cause of the condition in the remaining individuals is unknown.

The C9orf72, SOD1, TARDBP, and FUS genes are key to the normal functioning of motor neurons and other cells. It is unclear how mutations in these genes contribute to the death of motor neurons, but it is thought that motor neurons are more sensitive to disruptions in function because of their large size. Most motor neurons affected by ALS have a buildup of protein clumps (aggregates); however, it is unknown whether these aggregates are involved in causing ALS or are a byproduct of the dying cell.

In some cases of familial ALS due to mutations in other genes, studies have identified the mechanisms that lead to ALS. Some gene mutations lead to a disruption in the development of axons, the specialized extensions of nerve cells (such as motor neurons) that transmit nerve impulses. The altered axons may impair transmission of impulses from nerves to muscles, leading to muscle weakness and atrophy. Other mutations lead to a slowing in the transport of materials needed for the proper function of axons in motor neurons, eventually causing the motor neurons to die. Additional gene mutations prevent the breakdown of toxic substances, leading to their buildup in nerve cells. The accumulation of toxic substances can damage motor neurons and eventually cause cell death. In some cases of ALS, it is unknown how the gene mutation causes the condition.

The cause of sporadic ALS is largely unknown but probably involves a combination of genetic and environmental factors. Variations in many genes, including the previously mentioned genes involved in transmission of nerve impulses and transportation of materials within neurons, increase the risk of developing ALS. Gene mutations that are risk factors for ALS may add, delete, or change DNA building blocks (nucleotides), resulting in the production of a protein with an altered or reduced function. While genetic variations have been associated with sporadic ALS, not all genetic factors have been identified and it is unclear how most genetic changes influence the development of the disease. People with a gene variation that increases their risk of ALS likely require additional genetic and environmental triggers to develop the disorder.

Inheritance described in the linked summary

From: MedlinePlus Genetics

About 90 to 95 percent of ALS cases are sporadic, which means they are not inherited.

An estimated 5 to 10 percent of ALS is familial and caused by mutations in one of several genes. The pattern of inheritance varies depending on the gene involved. Most cases are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. Some people who inherit a familial genetic mutation known to cause ALS never develop features of the condition. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with a mutated gene do not.

Less frequently, ALS is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Because an affected person's parents are not affected, autosomal recessive ALS is often mistaken for sporadic ALS even though it is caused by a familial genetic mutation.

Very rarely, ALS is inherited in an X-linked dominant pattern. X-linked conditions occur when the gene associated with the condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males tend to develop the disease earlier and have a decreased life expectancy compared with females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Which doctor should you see?

The suggested department for discussing Amyotrophic Lateral Sclerosis is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.