New discovery may aid in early detection of rare genetic disease

Virginia Tech researchers discovered an indication hidden in the brain that may help doctors identify children suffering from a rare genetic disease earlier. Their findings were published recently in EMBO Molecular Medicine.

Leigh syndrome is a severe neurological disorder that affects the mitochondria, which are energy factories found in almost all the cells of the body. This disease typically appears in infancy and can progress rapidly, leading to limited treatment options and poor survival rates.

Prenatal tests for mitochondrial disorders like Leigh syndrome are not commonly administered.

If there's not any real sign that you have something wrong with you at birth, they're not going to recommend genetic testing or genetic counseling."

Alicia Pickrell, associate professor, School of Neuroscience, Virginia Tech

Without screening, children with Leigh syndrome appear to develop normally until 9 or 10 months old, when they start to display symptoms and quickly decline.

However, a recent clinical study from the Children's Hospital of Philadelphia showed that early signs of neurodevelopmental delay often can be seen before the disease starts to impact a patient's motor and respiratory functions.

When they learned about the early signs, Pickrell and her collaborators saw a way to help.

"The study is saying that these mutations don't impact these patients out of the blue. These children were born with them," Pickrell said.

Maybe, Pickrell said, we haven't used the right tools or looked at the right areas in the brain. Which means maybe there's a chance people with this disease could be identified - and someday treated - earlier.

Working with Paul Morton, assistant professor in the Virginia-Maryland College of Veterinary Medicine, and Sahitya Biswas, a student in the Translational Biology, Medicine, and Health Graduate Program, Pickrell was able to evaluate Leigh syndrome symptoms in a mouse model.

In their study, the researchers observed developmental defects and sluggish activity within specialized neural stem cells soon after birth. 

They identified a malformed area centered on a bundle of nerve fibers called the corpus callosum, which is Latin for "tough body." Using microscopy, researchers found a pattern of bad connections in this thick nerve tract that serves as the main line of communication between the left- and right-sides of the brain.

"From the data we've been collecting, it looks like it's just not developing the way it should," Pickrell said. "The neural stem cells aren't generating the types of cells they are supposed to."

But now that they know where to look, there's a path toward identifying children who suffer from Leigh Ssndrome earlier and getting them into clinical trials.