Types of ALS

Last updated March 8, 2023, by Marisa Wexler, MS
Fact-checked by Ines Martins, PhD

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that can be classified into different types based on factors like genetics, a patient’s family history, and the disorder’s early symptoms.

Across all types, ALS is marked by the loss of motor neurons, the nerve cells that control voluntary muscle movements, leading to symptoms like muscle weakness and trouble speaking.

Are there different types of ALS?

Muscle weakness and atrophy (wasting), resulting from progressive motor neuron degeneration, is a hallmark feature observed in all ALS cases, but the condition can be divided into different types based on specific characteristics.

There are two main methods used to classify the disease: one based on family history and the other on clinical onset.

ALS can be found among relatives in a family. Thus, based on whether or not a person has a family history, the disease can be divided into sporadic or familial ALS.

On the other hand, the disorder also can be classified as either limb-onset or bulbar-onset depending on which muscles in the body are first affected.

In addition to these main ALS types, patients can be classified based on their disease-related genetic mutations. There also are rarer types, such as juvenile ALS and an ALS-like disorder known as ALS-PDC, that share symptoms of other diseases.

While these classifications may be helpful for describing an individual’s disease, it’s important to note that ALS affects everyone differently. There can be a lot of variation in how the disease appears and progresses over time, even among individuals with the same types of ALS.

Classification by family history

While the causes of ALS remain incompletely understood, genetics are known to play a sizable role in influencing an individual’s risk of developing the disorder.

Because ALS-associated genetic mutations can be passed from parents to their biological children, the disease can run in families. If more than one person in a family has ALS, these patients are said to have familial ALS. Cases where there is no family history of the disease are referred to as sporadic ALS — with sporadic meaning that there’s no clear pattern.

Importantly, genetics play a role in both familial and sporadic ALS. The distinction is purely based on whether or not the affected individual is known to have biological family members who have or have had the disease.

In fact, some people with sporadic disease harbor ALS-associated mutations usually identified in familial disease, while specific disease-causing mutations are not seen in every case of familial ALS.

The term genetic ALS is sometimes used to refer to cases of ALS, either sporadic or familial, in which the patient harbors a known ALS-associated genetic mutation.

Familial ALS

Familial or inherited ALS accounts for about 10% of cases of the disease. ALS-associated mutations can be passed from parents to their biological children, and family members of ALS patients have a 3-10 times higher risk of developing the condition.

Mutations associated with familial ALS usually are inherited in an autosomal dominant manner, meaning that a person with an ALS mutation has a 50% chance of passing it to a biological child. However, inheriting a disease-linked mutation does not mean that a person is guaranteed to develop ALS; other environmental and lifestyle factors also are at play.

The specific mutations driving the disease are known in about 60% of familial ALS cases. In the remaining cases, the fact that the disease runs in the families suggests a genetic contribution, but specific disease-associated mutations have not been identified.

The most common disease-causing mutation, associated with 30% to 50% of familial ALS cases, is in a gene called C9ORF72. Mutations in the gene SOD1 account for another 10% to 20% of familial ALS cases, while mutations in the genes TARDBP and FUS are found in roughly 3% to 5% of familial ALS cases.

Sporadic ALS

The vast majority of people with ALS — about 90% of all patients — do not have any family members with the disease, and thus are classified as having sporadic ALS.

In these patients, biological and environmental factors are believed to play a more important role than genetics. Yet, about 10% of patients with sporadic ALS have a known ALS-associated mutation.

The most common mutations in these patients, found in about 7% to 10% of cases, are also in the C9ORF72 gene. SOD1 mutations are present in 1% to 2% of sporadic ALS patients, and mutations in other genes are generally detected in fewer than 1% of patients.

Classification by clinical onset

The early signs of ALS usually are quite mild and only affect one part of the body at first, before spreading to affect other body parts as the disease progresses. Depending on which body parts are affected first, ALS may be classified as limb-onset or bulbar-onset.

Limb-onset ALS

Limb-onset ALS is a form of the disease in which initial symptoms affect the muscles in the arms and hands, or the legs and feet. This type is observed in about two-thirds of ALS patients, and is sometimes referred to as spinal ALS.

When the upper limbs are first affected, the earliest symptom of ALS is usually weakness in the dominant hand, which can manifest as difficulty with writing or holding objects. In the lower limbs, initial ALS symptoms usually affect muscles in the calves, leading to balance issues and trouble walking.

Bulbar-onset ALS

In about one-third of patients, ALS first affects the bulbar muscles — a group of muscles in the head and neck that are important for coordinating movements of the mouth and throat. This form of the disease is known as bulbar-onset ALS.

The most common initial symptoms in bulbar-onset ALS are speech difficulties — such as trouble articulating words, slurred speech, or a hoarse voice — and trouble swallowing. Less commonly, first manifestations can include difficulty fully closing the mouth or trouble chewing.

Bulbar-onset ALS is more often diagnosed in women and in older people. While there can be a lot of variation from person to person in how ALS progresses, this form of the disorder tends to progress more rapidly than limb-onset ALS. Consequently, the expected survival for someone diagnosed with bulbar-onset ALS is typically shorter than for patients with limb-onset disease.

Other types of ALS

Juvenile ALS

In most people, ALS develops in middle or late adulthood. Juvenile ALS, meanwhile, refers to disease that develops in patients younger than age 25.

This form of ALS is extremely rare, affecting fewer than 1,000 people in the U.S.

The age at onset and progression of juvenile ALS varies considerably — some cases are extremely aggressive and lead to death in a few years, while other people with juvenile ALS may experience a slow progression of symptoms over the course of decades. Cognitive problems are less common in juvenile ALS compared with adult disease.

While disease-causing mutations are identified in around 10% of all adult-onset ALS cases, juvenile ALS has a greater genetic contribution, with about 40% of patients having a known gene mutation.

The most commonly affected genes include FUS, SETX, and ALS2. Other genes that have also been associated with juvenile forms of ALS include SPG11, SOD1, UBQNL2, SIGMAR1, and TARDBP.

While researchers are continuing to learn more about these rare subtypes of ALS, certain mutations have already been linked with specific patterns of disease progression. For example, scientists reported in 2021 a previously unknown subtype of juvenile ALS caused by mutations in the SPLTC1, which resulted in disease onset in early childhood.

ALS-parkinsonism-dementia complex 1 (ALS-PDC)

ALS-parkinsonism-dementia complex 1, called ALS-PDC for short, is  a rare disorder that can present with a range of neurological symptoms, including some, like muscle weakness and wasting, that are typical of all forms of the disease.

ALS-PDC also can cause symptoms that are more commonly seen in Parkinson’s disease, such as slowed movements, rigidity, and tremors. People with ALS-PDC also commonly develop dementia, typically seen as cognitive and behavioral problems that substantially impair patients’ daily life.

The disorder is sometimes called Guam disease because it was first recognized among indigenous peoples on the Pacific island of Guam. In addition to Guam, ALS-PDC has been reported in other regions in the Pacific, particularly the Kii Peninsula of Honshu Island in Japan, and Papua, Indonesia, on the western side of the island of New Guinea.

Research has suggested that ALS-PDC is likely caused by exposure to certain toxins that are found in seeds of cycad plants. These plants have been used for food and medicines in these regions, particularly in times of food scarcity such as during and after World War II. In recent decades, the incidence of ALS-PDC has decreased substantially, tied to reduced consumption of cycad seeds.

ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.