Cause of Rare Form of Pediatric Leukoencephalopathy Discovered

A Collaborative Effort

An international team of researchers has just uncovered the genetic cause for an ultra-rare form of leukoencephalopathy. Leukoencephalopathy refers to a family of conditions which affect the white matter in the brain (myelin) as well as the patient’s nerve cells.

This research was led by the Rady Children’s Institute for Genomic Medicine (RCIGM) in California.

Mathilde’s Story

Mathilde was born at the McGill University Health Centre (RI-MUHC) in Montreal in 2013 with an abnormally small head. Doctors were concerned and immediately sent her to the ICU where she received neurological testing. The tests showed her brain had not developed as it should and her myelin was atypical. She was diagnosed with a rare and unidentified form of leukoencephalopathy. With no treatment options available, she only lived to be 2 and a half months old.

With the help of RCIGM, researchers at RI-MUHC now know the cause of Mathilde’s leukoencephalopathy. They confirmed her condition was related to the mutations in the VARS gene.

The Discovery

Mathilde’s condition was investigated along with six other children who had brain abnormalities and had suffered epileptic seizures. Using blood tests, whole exome, and whole genome sequencing, mutations in the VARS gene were uncovered. Mutations in this particular gene have never before been linked to disease.

The VARS mutation causes damage to the enzymes responsible for creating proteins which contain valine, an amino acid. This type of damage is associated with neuropathy, microcephaly, and other rare conditions. What this means, is that patients with a VARS mutation could potentially benefit from a therapy which restores valine.

The children in this study were evaluated in Cairo, Montreal, and San Diego. Hospitals in Hong Kong, Amsterdam, Egypt, and Qatar also helped in the confirmation of the findings. This collaborative effort was an essential part of this research, especially considering the fact that the patients were dispersed geographically.

The Value of Diagnosis

Understanding the root cause of a patient’s symptoms is truly the key to providing them effective treatments. However, for far too many children living with rare diseases, the cause of their ailment is never identified.

Even for the children who sadly cannot be saved, learning the cause of their pain can help families grieve. Furthermore, participating in research can help them feel they are making a difference in the lives of future patients. This is how Mathilde’s parents feel.

“It felt good to know that our daughter could help other children and the scientific community at large.”

Now researchers are looking into gene therapy and valine as a dietary supplement as potential treatments for this form of leukoencephalopathy. Since they now understand which protein is being altered in this condition, they are able to examine what therapies may help specifically restore this exact protein.

You can read the full results from this study, published in Nature Communications here.

You can also read a summary of this study here.


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