by DedMityay / Canva
A new neurological disorder that causes problems with speech and motor coordination has been identified in three children in the United States.
Researchers from the National Institutes of Health’s National Human Genome Research Institute (NHGRI) and the Undiagnosed Diseases Program believe that the disease is caused by a genetic mutation which affects the ability of neurons in the brain to properly perform a cell recycling function called autophagy.
In addition to helping people affected by the disease, the scientists responsible for the discovery – the results of which were recently published in npj genomic medicine – We hope this discovery could help other diseases in which autophagy is involved, such as Alzheimer’s, said the New Atlas.
The first child in the study developed symptoms at age three. He had an unsteady gait and impaired coordination. As he grew older he began to have seizures, impaired reflexes and speech patterns that were only 60-75% intelligible.
At the age of nine and a half, he was diagnosed with attention deficit hyperactivity disorder (ADHD). mild cognitive impairment, and oppositional defiant disorder, a condition characterized by irritability and anger, as well as arguments with parents and other authority figures. The boy has a sister who, despite developmental problems, grew up with no symptoms of the disease.
The other two children are sisters. One of them started to move her arms abnormally, stumbles and has periods of staring, with a mild learning disability and speech difficulties. The other sister also had problems with motor control that eventually resolved, although she still had problems articulating words.
Examining the children’s health records, the researchers found that all had mutations in a gene known as ATG4D. Scientists knew from a 2015 study that a mutation in this gene caused problems with motor control and eye movement in Lagotto Romagnolo dogs, but had not yet linked the mutation to humans.
The team found that the affected cells were unable to perform autophagy, a process in which all cells break down old or damaged proteins for reuse when needed.
Enhanced autophagy has been linked to a narrowing of blocked arteries and longer lifespan in mice. Research published in 2022 shows that the process of autophagy can be manipulated to reduce the amount of plaque-causing proteins that build up in the brain, which ultimately cause Alzheimer’s disease.
Interestingly, the researchers found that the ATG4D mutation in the children’s affected skin cells did not interfere with autophagy. Only in the brain did the mutation alter the cellular recycling system.
“The brain is so complex and neurons have very specialized functions”, said May Christine Malicdan, NHGRI scientist and senior author of the study. “To match these functions, different neurons use different genes, so changes in genes can have big effects on the brain.”
Because autophagy is implicated in both Alzheimer’s and Parkinson’s disease, the researchers hope their work will lead to breakthroughs in the investigation of these two conditions.
“This is the million dollar question in rare disease research. These can help us understand biological pathways so we can better understand how contribute to other rare and common conditions’.the researcher said.
ZAP //
