Diagnosing Emerging Disorders

How do you look for the cause of a brand new medical problem?
16 October 2013


Brain development requires a molecule wrongly written off as 'non-essential', scientists in the US have Puzzled doctordiscovered.

Patients with a newly-discovered brain disorder were found to be deficient in a chemical that can be obtained from food, but is not required because the body can make it itself.

The research, published in the journal Neuron, also revealed the power of genetic sequencing in rapidly identifying the cause of new and unstudied disorders.

"Patients from two different families had a very unusual presentation that did not look like any known syndrome, but that looked similar to one another", said Professor David Goldstein, at Duke University.

The children had reduced head growth, developmental delay and seizures.

"We had the idea we might be able to find the genetic basis of this new syndrome using next generation sequencing to find mutations in the patients," explained Goldstein.

To find the cause, the researchers studied the genetic variation between the children, looking for mutations not found in the general population. Between the two families, the only common mutation was in a gene that encodes an enzyme for producing protein building blocks.

The enzyme, asparagine synthetase, produces a small amino acid molecule called asparagine, labelled 'non-essential' because it is not a dietary necessity.

Separately, researchers at the University of Montréal had encountered further cases of the unknown disorder, also caused by defective asparagine synthetase.

"You always expect to find multiple observations of the consequences of mutation in any given gene", added Goldstein. "Anything that can happen in the human genome not only does happen somewhere in the world, but it happens repeatedly."

It remains unclear why defective asparagine production is harmful to the brain. It may result in toxic build up because the pathway is not working correctly, or asparagine may be required in higher levels in the nervous system.

The work has opened up research into the role of other 'non-essential' components in brain development. Defective production of these components has been linked to many neurological problems.

The detrimental effects of these genetic disorders might be reduced by altered diet. Recent experiments in mice suggest that non-essential food supplementation may prevent developmental damage.

"That's what I think is most encouraging about this kind of genetics", said Goldstein. "They can tell you in an underlying biochemical sense what's wrong, and that at least puts you on a path to figuring out how you can do something about it."



Add a comment