More Health:

April 07, 2016

CHOP researchers name new syndrome that causes rare intellectual disability

Scientists develop potential amino acid treatment based on principles of precision medicine

CHOP Disabilities
CHOP Exterior JVinocur/Wikimedia Commons

Children's Hospital of Philadelphia (CHOP)

Pediatric researchers at the Children's Hospital of Philadelphia have identified a new syndrome that causes a rare intellectual disability and may be treatable through an amino acid supplement that relies on the latest advances in precision medicine.

Scientists from CHOP's Center for Applied Genomics (CAG) collaborated with an international team from five countries to complete a series of cell studies that examined a specific gene change found in children with developmental delays. By focusing in on the TBCK gene, previously linked to intellectual disability in a single-family Saudi study, researchers were able to determine that clinical symptoms found in affected children were traceable to the same genetic mutations.

"Intellectual disability is a common diagnosis, but it includes many different diseases, with multiple genetic causes, and few targeted therapies,” said first author Elizabeth Bhoj, a Genetics fellow in the CAG. “This study may represent an early step toward the types of precision medicine treatment that may become more common as we draw on genomic research.”

To complete the study, DNA samples were taken from 13 affected children who came from nine unrelated families. To cross-check results, samples were also taken from the children's healthy parents. Four pairs of siblings in the study all possessed symptoms ranging from moderate to severe developmental delays and low muscle tone, while five of the children experienced seizures.

Despite variations in clinical symptoms among the patients, all of them had mutations to the TBCK gene (TBC1-domain-containing kinase), discovered through whole-exome sequencing. None of the parents in the study had an intellectual disability, yet they all carried the same gene mutation inherited by their children as a recessive trait from both parents.

The TBCK gene, which codes for the TBCK protein, works to regulate signals on the mTOR pathway and has previously been connected to epilepsy, autism and intellectual disability with evidence signal abnormalities. The study shows that the affected children, all of whom had lower levels of mTOR signaling and the TCBK protein, responded favorably to leucine, an amino acid that when added to cell cultures increased mTOR signaling in patients' cells.

Scientists have proposed calling the condition TBCK-related ID syndrome.

Senior study author and CAG director Hakon Hakonarson said the findings, which can be likened to dietary modifications used to manage other conditions, reinforce the promise of modern genetic approaches to uncovering disease.

“Such molecular phenotyping can help clarify disease relationships and inform future treatments, in keeping with our precision medicine focus.”

Bhoj added that the next step will be a pilot study that tests the effects of leucine supplements in children identified with TBCK-related ID syndrome.

The full study, published in the April edition of the American Journal of Human Genetics, can be accessed here.

Follow us

Health Videos