05 June 2015

WA researcher identifies new rare disease

A WA Health clinician has discovered a new and rare genetic disease.

In the highly-respected American Journal of Medical Genetics, Dr Gareth Baynam, a clinical geneticist based at King Edward Memorial Hospital, has documented the first case of a family with a mutation in the MTOR gene – a gene that regulates how cells grow, divide and function.

The gene fault was identified in 3 children in the family, each of whom was born with severe medical problems that affected their ability to learn and the structure of their bodies, including some internal organs.

The findings of Dr Baynam and his colleagues bring to an end a decade-long diagnostic odyssey for the family, during which time the children underwent numerous tests to try to identify the cause of their condition.

Dr Baynam says that while the children will always have significant medical problems, there are compelling reasons for establishing the cause of such rare conditions.

“For a start it gives the family a sense of closure. It means they know the cause of the condition and they can stop looking,” he says.

“When things go wrong, people look for reasons; they want certainty. Without a diagnosis, the family would always have been searching for answers.”

Dr Baynam’s findings also mean the family will no longer be circulating through the medical system looking for an answer and for the children, there will be no need for further tests to try to identify the cause of their condition.”

Most importantly however, identifying the underlying cause paves the way for treatment.

“We were fortunate in this case to have been able to identify an existing drug that we may be able to use in the future to treat the children and the good news is that it’s a medication that is relatively inexpensive and widely available.”

With the cost of developing a new drug being about $1.2 billion, Dr Baynam says the potential to use an existing medication, referred to as 'drug repurposing', is a real bonus to families, the pharmaceutical sector and to the health system.

Dr Baynam saw the children from early in their lives. He was confident their condition had an underlying genetic cause and had an idea of the sort of condition it could be.

“But after exhausting all tests available to us at the various times we saw the family, we could still not confirm a diagnosis. Not having an answer was hard for the family as well as those of us in the clinical services who were constantly hitting dead ends and having to find new avenues to explore.”

Recently, new genetic technology called next generation sequencing became available.

Based on the combination of findings in the family, the team applied this new technology to design a test that maximised the family’s chances of getting a result. It paid off.

“We found something,” he says.

“But we had to be sure we had the correct answer. This was a challenge because nobody had described faults in this gene in families anywhere in the world.”

Adding to the challenge was the fact that the children were Aboriginal and there was no accumulated genomic reference material for Aboriginal children.

“Our ability to interpret what we had discovered was hindered because we didn’t have that base understanding of the range of normal from which to work,” he said.

“We didn’t know if it really was rare or whether it was something common in the Aboriginal population that had just not been documented.”

That dearth of Aboriginal genomic reference material meant Dr Baynam needed an alternative means of verifying his result.

Finding somebody to perform the time-consuming and highly specialised – but necessary – functional test however, was another challenge. After scouring the globe for a laboratory with the expertise and willingness to do the test, he eventually found a group in Canberra.

The test, which involved introducing the gene fault seen in the family into a cell in the laboratory, provided Dr Baynam with the proof he needed. The team performing the studies in Canberra then went a step further, giving the drug rapamycin to the cells. The rapamycin reversed the effect of the gene fault in those cells, providing further proof of the genetic cause of the children’s disorder and a potential drug to treat the children.

Dr Baynam said the prolonged process involved in confirming a diagnosis for the family highlighted the difficulties and health inequities posed by the lack of genomic information and reference data for Aboriginal people. Had such data been available, a confirmed diagnosis may have been possible up to 15 months earlier.

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