Jan 5, 2011 10:46 GMT  ·  By

Professor John Rasko from the University of Sydney's Centenary Institute led an international team of researchers from the University of Sydney, Australian National University, Université de Sherbrooke in Canada and Royal Prince Alfred Hospital, and identified gene mutations that affect kidney function, leading to a rare kidney disorder called dicarboxylic aminoaciduria (DA).

This same gene is crucial for normal brain function too, and has been connected with obsessive-compulsive disorder (OCD).

These findings could open the way to an earlier diagnosis of children who could be at risk of early onset OCD, through a simple, non-invasive urine test conducted routinely on newborns.

Professor Rasko is Head of Gene and Stem Cell Therapy at the Centenary Institute, Head of Cell and Molecular Therapies at Royal Prince Alfred Hospital and a Professor at Sydney Medical School, University of Sydney.

He explained that “people with DA can be identified through a simple urine test that detects high levels of glutamate and aspartate.

“This simple, non-invasive test is used regularly for screening newborns for other serious genetic disorders.

“If this idea is confirmed in clinical trials, a simple urine test might be used to screen young children with a family history of OCD to identify anyone who may be at risk of early onset OCD.”

Leading OCD expert Dr Mairwen Jones from the University of Sydney said that “early onset OCD is a debilitating condition that affects about 3% of Australians.

“It is the most intractable and disabling of the anxiety disorders.

“OCD imposes a marked reduction in quality of life, an increased suicide rate and negative economic consequences to individuals and the community.

“It can begin as early as five years of age and it can be difficult to diagnose.

“Children with early onset OCD often live with the disorder undiagnosed and untreated for a number of years and often even into adulthood.

“The earlier we can diagnose OCD the sooner we can start treatment to manage the obsessive and compulsive behaviors.

“These findings are very exciting news as it will give us an easy way to identify children from families with OCD history who may have a personal risk of developing the disorder.”

Professor Rasko and Dr Charles Bailey from the Centenary Institute and lead researchers on the study, identified mutations in the gene SLC1A1.

This gene encodes a protein pump that passes important amino acids from our food into the kidney, and the human brain has an identical pump, that also controls the movement of the same amino acids, making them act as neurotransmitters.

After analyzing mutant pumps in affected families in this study, the researchers concluded that they were severely or completely impaired in their ability to transport these important amino acids in the kidney.

“These findings prove for the first time that SLC1A1 is the affected gene in dicarboxylic aminoaciduria and demonstrate the crucial role that SLC1A1 plays in the kidney's ability to process the essential amino acids glutamate and aspartate,” said Professor Rasko.

“Dicarboxylic aminoaciduria is a rare kidney disorder but this discovery may provide us with a clue to understanding OCD that affects approximately 3% of Australians.

“Due to the crucial role of SLC1A1 in normal brain function, the findings also have major implications for a likely genetic cause of some brain disorders like obsessive-compulsive disorder.

“During the past few decades studies have revealed that OCD has a strong genetic component.

“Various genetic studies have linked OCD to SLC1A1 and other studies have also implicated abnormal brain glutamate activity in OCD.

“However, there has been no physical proof of how SLC1A1 is likely to cause OCD.

“Our research is a major first step towards bridging this gap as we have discovered those genetic defects that could impair the normal functioning of the neurotransmitter glutamate in the brain,” added Professor Rasko.

The researchers believe that the results of this study could help not only people with DA, but also those at risk of early onset OCD – that can start in kids at the age of 5 or 6.

This research completes the molecular profiling of all five principal inherited kidney disorders – cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria and dicarboxylic aminoaciduria.

This research was funded by the Australian National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), University of Sydney Bridging Support Grant, Rebecca L. Cooper Foundation and Cure the Future Foundation.

The findings are published today in the Journal of Clinical Investigation.

Here is something to give you a clue of the way OCD manifest: