Mutations More Prevalent in ALS than Thought


Genetic mutations likely case more cases of amyotrophic lateral sclerosis (ALS) than previously thought, according to a new study in Annals of Neurology.

Genetic mutations likely cause more cases of amyotrophic lateral sclerosis (ALS) than previously thought, according to a new study in Annals of Neurology.

About 90% of ALS patients have sporadic ALS, meaning they have no family history of the disease. Until now scientists had thought only 1 in 10 cases of sporadic ALS was related to genetic mutations.

“To our surprise we found that 26% of sporadic ALS patients had potential mutations in one of the known ALS genes we analyzed,” said Matthew Harms MD, assistant professor of neurology at Washington University in St. Louis, MO, a co-senior author of the paper.

With colleagues at Cedars-Sinai Medical Center in Los Angeles, CA, he also found that the number of mutated genes influences the age at which ALS first appears. There are at least 30 genes in which mutations can cause the disease. Some of these mutated genes can be inherited.

To look for 17 known ALS genes in the DNA of 391 patients with ALS, the researchers at Washington University devised a new sequencing technique.

“It is also possible that these mutations could be combining with environmental factors linked to ALS,” said senior co-author Robert Baloh, MD, PhD, associate professor of neurology at Cedars-Sinai. That could explain cases where family members of a patient with ALS share those mutations but do not come down with the disease.

The more mutations a person has, the earlier he or she will develop ALS symptoms, the researchers said.

The average age of onset for patients with one mutation was 61, but when a patient had more mutations, that age dropped to 51.

According to the ALS Association, there are about 5,600 people in the US diagnosed with ALS annually. The incidence of the disease is 2 per 100,000 population and there are about 30,000 people in the US living with the disease. Life expectancy averages 2 to 5 years from time of diagnosis but varies with 5% living for 20 years with the disease.

The drug riluzole (Rilutek/Sanofi) has shown some efficacy in delaying progression of symptoms including lengthening the time before patients will need a tracheostomy to breath.

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